PTENc.106G>CPathogenic

Print report

Variant interpretation report

PTEN c.106G>C, p.(Gly36Arg)

NM_000314.8:c.106G>C NP_000305.3:p.(Gly36Arg) View identifiers

Classification

Pathogenic

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.

Pathogenic.A pathogenic classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About PTEN

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 strong (pathogenic) · 1 moderate (pathogenic) · 4 supporting (pathogenic)
Expert rules: ClinGen PTEN VCEP v3.2.0
Other laboratories (ClinVar): 1 Pathogenic · 1 Uncertain significance
Pipeline record: 15 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PS1 (strong): NM_000314.8:c.106G>C encodes p.Gly36Arg (G36R). A different nucleotide substitution at the same codon, NM_000314.8:c.106G>A, also encoding p.Gly36Arg, is established as pathogenic: ClinVar 3-star expert panel classifies it as Likely Pathogenic (VCV000189400), and it has been reported in a Cowden syndrome proband with bilateral breast cancer (PMID:10772390) with demonstrated 90% loss of phosphatase activity. The VCEP PS1 rule is satisfied: same amino acid change as a previously established pathogenic variant regardless of nucleotide change.
PS3 (moderate): The PTEN G36R variant has a cumulative fitness score (Cum_score) of -2.69 in the Mighell et al. 2018 (PMID:29706350) saturation mutagenesis functional assay (mmc2.xlsx Table S2), meeting the VCEP PS3_Moderate threshold of Cum_score <= -1.11. High_conf = True and the variant Pass SE Filter. This is a massively parallel phosphatase activity assay directly testing all possible PTEN missense variants. The damaging functional effect is corroborated by PMID:10772390 (90% loss of phosphatase activity for G36R from c.106G>A) and PMID:21828076 (G36R tested among PHTS-associated mutations in yeast in vivo model, showing loss of function).
PM2 (supporting): NM_000314.8:c.106G>C is absent from all large population databases: gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (HostSeq genomes). The VCEP PTEN PM2 rule applies at supporting strength when a variant is absent or present at <0.00001 (0.001%) allele frequency in gnomAD or another large sequenced population.
PP2 (supporting): PTEN has a low rate of benign missense variation and missense variants are a common mechanism of disease in PTEN hamartoma tumor syndrome. NM_000314.8:c.106G>C is a missense variant in a gene meeting these criteria, satisfying the VCEP PTEN PP2 rule at supporting strength.
PP3 (supporting): Multiple lines of in silico evidence support a deleterious effect. The REVEL score is 0.995, which exceeds the VCEP PTEN PP3 threshold of >0.7 for missense variants. The BayesDel score is 0.617, providing additional orthogonal support for a damaging prediction.
PP5 (supporting): Expert panel Clingen PTEN Variant Curation Expert Panel, Clingen classified as Likely pathogenic.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is ClinGen PTEN VCEP v3.2.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 6 Benign evidence criteria: 0

Pathogenic criteria applied · 6

PS1Strong

PS1 · strong

NM_000314.8:c.106G>C encodes p.Gly36Arg (G36R). A different nucleotide substitution at the same codon, NM_000314.8:c.106G>A, also encoding p.Gly36Arg, is established as pathogenic: ClinVar 3-star expert panel classifies it as Likely Pathogenic (VCV000189400), and it has been reported in a Cowden syndrome proband with bilateral breast cancer (PMID:10772390) with demonstrated 90% loss of phosphatase activity. The VCEP PS1 rule is satisfied: same amino acid change as a previously established pathogenic variant regardless of nucleotide change.

PS3Moderate

PS3 · moderate

The PTEN G36R variant has a cumulative fitness score (Cum_score) of -2.69 in the Mighell et al. 2018 (PMID:29706350) saturation mutagenesis functional assay (mmc2.xlsx Table S2), meeting the VCEP PS3_Moderate threshold of Cum_score <= -1.11. High_conf = True and the variant Pass SE Filter. This is a massively parallel phosphatase activity assay directly testing all possible PTEN missense variants. The damaging functional effect is corroborated by PMID:10772390 (90% loss of phosphatase activity for G36R from c.106G>A) and PMID:21828076 (G36R tested among PHTS-associated mutations in yeast in vivo model, showing loss of function).

PM2Supporting

PM2 · supporting

NM_000314.8:c.106G>C is absent from all large population databases: gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (HostSeq genomes). The VCEP PTEN PM2 rule applies at supporting strength when a variant is absent or present at <0.00001 (0.001%) allele frequency in gnomAD or another large sequenced population.

PP2Supporting

PP2 · supporting

PTEN has a low rate of benign missense variation and missense variants are a common mechanism of disease in PTEN hamartoma tumor syndrome. NM_000314.8:c.106G>C is a missense variant in a gene meeting these criteria, satisfying the VCEP PTEN PP2 rule at supporting strength.

PP3Supporting

PP3 · supporting

Multiple lines of in silico evidence support a deleterious effect. The REVEL score is 0.995, which exceeds the VCEP PTEN PP3 threshold of >0.7 for missense variants. The BayesDel score is 0.617, providing additional orthogonal support for a damaging prediction.

PP5Supporting

PP5 · supporting

Expert panel Clingen PTEN Variant Curation Expert Panel, Clingen classified as Likely pathogenic.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Pathogenic

Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework: matched Rule8 (1 Pathogenic.Strong + 1 Pathogenic.Moderate + Pathogenic.Supporting >=4) with applied criteria: PS1 strong, PS3 moderate, PM2 supporting, PP2 supporting, PP3 supporting, PP5 supporting; maps to Pathogenic.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.270 maximum delta

Recorded SpliceAI maximum delta score: 0.270. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · PP3 → SpliceAI ↗

ClinVar submissions

2 reported laboratory submissions

1 Pathogenic · 1 Uncertain significance. ClinVar API review status: reviewed by expert panel.

Applied · PP5 → ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Loss-of-function; curated oncogenicity label: Oncogenic.

Applied · PS3 → OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

1 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV100909550, n = 1 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under ClinGen PTEN VCEP v3.2.0, with the data and sources behind each one.

29 criteria with recorded statuses: 6 met · 15 not met · 0 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_000314.8:c.106G>C (p.Gly36Arg) is a missense variant in PTEN exon 2. It is absent from all large population databases (gnomAD v2.1, v4.1, gnomAD-Canada).

The same amino acid change (p.Gly36Arg) from a different nucleotide substitution (c.106G>A) is classified as Likely Pathogenic by the ClinGen PTEN Variant Curation Expert Panel in ClinVar (VCV000189400, 3-star review).

Saturation mutagenesis functional data from Mighell et al. 2018 (PMID:29706350) demonstrate a severe damaging effect: G36R cumulative fitness score is -2.69 (threshold for PS3_Moderate is <= -1.11).

Additional functional studies corroborate the damaging effect: PMID:10772390 demonstrated 90% loss of phosphatase activity for G36R, and PMID:21828076 confirmed loss of function in a yeast in vivo assay.

In silico predictions uniformly support pathogenicity: REVEL score 0.995 and BayesDel score 0.617.

Applying the ClinGen PTEN VCEP v3.2.0 combination rules: PS1 (strong) is met (same amino acid change as established pathogenic c.106G>A); PS3_Moderate is met (Mighell et al. Cum_score -2.69 <= -1.11); and multiple supporting criteria are met (PM2_Supporting, PP2, PP3, PP5). Per VCEP Rule 11, one strong criterion (PS1) plus one moderate criterion (PS3_Moderate) is sufficient for a Likely Pathogenic classification.

Met · 6

PS1 StrongNM_000314.8:c.106G>C encodes p.Gly36Arg (G36R). A different nucleotide substitution at the same codon, NM_000314.8:c.106G>A, also encoding p.Gly36Arg, is established as pathogenic: ClinVar 3-star expert panel classifies it as Likely Pathogenic (VCV000189400), and it has been reported in a Cowden syndrome proband with bilateral breast cancer (PMID:10772390) with demonstrated 90% loss of phosphatase activity. The VCEP PS1 rule is satisfied: same amino acid change as a previously established pathogenic variant regardless of nucleotide change. Details ▾Hide ▴

Evidence considered

Same amino acid change (p.Gly36Arg) as NM_000314.8:c.106G>A
which is classified Likely Pathogenic by ClinGen PTEN VCEP in ClinVar (VCV000189400
3-star)
PMID:10772390 reports c.106G>A (G36R) in a 47-year-old female with Cowden syndrome
bilateral breast carcinoma at ages 28 and 31
and demonstrated 90% loss of phosphatase activity in the recombinant mutant protein

Sources

clinvar ↗PMID:10772390 ↗

PS3 ModerateThe PTEN G36R variant has a cumulative fitness score (Cum_score) of -2.69 in the Mighell et al. 2018 (PMID:29706350) saturation mutagenesis functional assay (mmc2.xlsx Table S2), meeting the VCEP PS3_Moderate threshold of Cum_score <= -1.11. High_conf = True and the variant Pass SE Filter. This is a massively parallel phosphatase activity assay directly testing all possible PTEN missense variants. The damaging functional effect is corroborated by PMID:10772390 (90% loss of phosphatase activity for G36R from c.106G>A) and PMID:21828076 (G36R tested among PHTS-associated mutations in yeast in vivo model, showing loss of function). Details ▾Hide ▴

Evidence considered

Mighell et al. 2018 saturation mutagenesis: G36R Cum_score = -2.69296249 <= -1.11 (High_conf=True
Pass SE Filter)
PMID:10772390: G36R (from c.106G>A) recombinant protein showed 90% loss of phosphatase activity
PMID:21828076: G36R tested in yeast in vivo model among PHTS-associated mutations
confirmed loss of function

Sources

vcep_mmc2PMID:10772390 ↗PMID:21828076 ↗

PM2 SupportingNM_000314.8:c.106G>C is absent from all large population databases: gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (HostSeq genomes). The VCEP PTEN PM2 rule applies at supporting strength when a variant is absent or present at <0.00001 (0.001%) allele frequency in gnomAD or another large sequenced population. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1
Absent from gnomAD v4.1
Absent from gnomAD-Canada v1.0

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PP2 SupportingPTEN has a low rate of benign missense variation and missense variants are a common mechanism of disease in PTEN hamartoma tumor syndrome. NM_000314.8:c.106G>C is a missense variant in a gene meeting these criteria, satisfying the VCEP PTEN PP2 rule at supporting strength. Details ▾Hide ▴

Evidence considered

PTEN is established as a gene with low benign missense variation rate and missense variants as a common disease mechanism

Sources

cspec ↗

PP3 SupportingMultiple lines of in silico evidence support a deleterious effect. The REVEL score is 0.995, which exceeds the VCEP PTEN PP3 threshold of >0.7 for missense variants. The BayesDel score is 0.617, providing additional orthogonal support for a damaging prediction. Details ▾Hide ▴

Evidence considered

REVEL score 0.995 > 0.7 (VCEP threshold)
BayesDel score 0.617 (supports damaging prediction)

Sources

revelbayesdel

PP5 SupportingExpert panel Clingen PTEN Variant Curation Expert Panel, Clingen classified as Likely pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar VCV000189400: Likely Pathogenic
reviewed by expert panel (ClinGen PTEN VCEP
3-star)
ClinVar expert panel classification

Sources

clinvar ↗

Not met · 15 · evaluated, threshold not reached

PS2 No de novo observation has been identified for this variant. Parental testing data confirming de novo occurrence of NM_000314.8:c.106G>C in a patient with PTEN hamartoma tumor syndrome and no family history is absent from all reviewed sources. Details ▾Hide ▴

Still missing

No de novo observation data available for this variant

PS4 Only a single proband with this variant has been identified in the reviewed literature (PMID:10772390 reports a Cowden syndrome patient with c.106G>A, same amino acid change). The VCEP PTEN PS4 rule requires a specificity score of at least 1-1.5 for supporting evidence, >=2 for moderate, >=4 for strong, and >=16 for very strong. A single proband does not meet any VCEP PS4 threshold. Details ▾Hide ▴

Evidence considered

PMID:10772390: one proband with Cowden syndrome and G36R (c.106G>A) — insufficient for VCEP PS4 proband count thresholds

Still missing

Additional probands with phenotypic data needed to calculate VCEP PS4 specificity score

Sources

PMID:10772390 ↗

PM1 G36 is located in the N-terminal region of PTEN (position 36 of NP_000305.3). The PTEN VCEP defines PM1 specifically for residues in the catalytic motifs: 90-94 (WPD-loop), 123-130 (P-loop), and 166-168 (TI-loop). G36 is outside these defined critical functional domains. While cancerhotspots.org identifies this as a statistically significant hotspot in somatic contexts, the VCEP has restricted PM1 application to the specified catalytic motif residues for germline interpretation. Details ▾Hide ▴

Evidence considered

VCEP PTEN PM1 defined for catalytic motifs 90-94
123-130
166-168
G36 (position 36) is outside these ranges

Sources

cspec ↗

PM5 No different missense variant at residue G36 has been independently classified as Pathogenic or Likely Pathogenic in ClinVar with expert panel review to satisfy the VCEP PM5 rule. Per the VCEP PTEN PM5 rule, a missense change at an amino acid residue where a different missense change has been determined to be P/LP, with the interrogated variant having a BLOSUM62 score equal to or less than the known variant, is required. Details ▾Hide ▴

Evidence considered

pm5_candidates search returned no same-residue comparator variants meeting VCEP PM5 criteria

Still missing

Evaluation of other G36 ClinVar variants for independent P/LP classification by non-VCEP submitters

Sources

pm5_candidates

PM6 No de novo observation has been identified for NM_000314.8:c.106G>C. No assumed or confirmed de novo occurrence in a patient with PTEN hamartoma tumor syndrome and no family history is documented in any reviewed source. Details ▾Hide ▴

Still missing

No de novo data available for this variant

PP1 No co-segregation data are available for this variant. The VCEP PTEN PP1 rule requires at least 3-4 meioses for supporting level; no family studies with segregation analysis have been identified. Details ▾Hide ▴

Still missing

No segregation data available

BA1 The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. The VCEP PTEN BA1 threshold of filtering allele frequency >0.00056 (0.056%) is not met. Details ▾Hide ▴

Evidence considered

gnomAD filtering allele frequency is 0
below BA1 threshold of >0.056%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The variant is absent from gnomAD. The VCEP PTEN BS1 thresholds are not met: the allele frequency is 0, which is below the BS1_Strong threshold of >=0.000043 (0.0043%) and the BS1_Supporting threshold of >=0.0000043 (0.00043%). Details ▾Hide ▴

Evidence considered

gnomAD allele frequency is 0
below all VCEP BS1 thresholds

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No homozygous observations of this variant have been identified in healthy or PHTS-unaffected individuals. The VCEP PTEN BS2 rule requires observation in the homozygous state in a healthy or PHTS-unaffected individual. Details ▾Hide ▴

Evidence considered

Variant is absent from gnomAD
no homozygous observations identified

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS3 The functional data demonstrate a damaging effect, not a benign effect. G36R has a cumulative fitness score of -2.69 in the Mighell et al. 2018 saturation mutagenesis assay (mmc2.xlsx), which meets PS3_Moderate criteria rather than BS3. The VCEP PTEN BS3_Supporting threshold requires phosphatase activity >0, which is not met. Details ▾Hide ▴

Evidence considered

G36R Cum_score = -2.69 <= -1.11 (damaging
not benign)
BS3 threshold of >0 not met

Sources

vcep_mmc2

BS4 No segregation data are available to evaluate lack of segregation. No family studies showing non-segregation of this variant with disease have been identified. Details ▾Hide ▴

Still missing

No segregation data available

BP2 No observations of this variant in trans with a pathogenic or likely pathogenic PTEN variant, nor three or more observations in cis or unknown phase with different P/LP PTEN variants, have been identified. Details ▾Hide ▴

Still missing

No phase data available

BP4 Computational evidence does not suggest a benign impact. The REVEL score is 0.995 (well above the VCEP BP4 threshold of <0.5 for missense variants). The SpliceAI maximum delta score is 0.27, which is above the 0.2 threshold for benign splicing prediction. BP4 is not met. Details ▾Hide ▴

Evidence considered

REVEL score 0.995 > 0.5 (BP4 threshold not met)
SpliceAI max delta 0.27 > 0.2 (splicing impact cannot be excluded)

Sources

revelspliceai ↗

BP5 No case has been identified where this variant was found in a patient with an alternate molecular basis for disease. The VCEP PTEN BP5 rule requires at least two such cases with a highly penetrant alternate gene/disorder and no phenotypic overlap with PTEN. Details ▾Hide ▴

Still missing

No alternate molecular basis cases identified

BP7 NM_000314.8:c.106G>C is a missense variant (p.Gly36Arg), not a synonymous or intronic variant. The VCEP PTEN BP7 rule applies only to synonymous or intronic variants at or beyond +7/-21 for which splicing prediction algorithms predict no impact to the splice consensus sequence. Details ▾Hide ▴

Evidence considered

c.106G>C is a missense substitution
not a synonymous or intronic variant

Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/APVS1 is not applicable to missense variants. The PTEN VCEP PVS1 decision tree (NM_000314.8) is limited to null variants: nonsense, frameshift, canonical GT-AG splice site disruptions, and single/multi-exon deletions with positional assessment relative to p.D375 (c.1121). NM_000314.8:c.106G>C is a missense substitution (p.Gly36Arg) and does not fall into any PVS1-eligible null variant bucket. Details ▾Hide ▴

Sources

vcep_pvs1_decisiontree_ptenpvs1_variant_assessment

PM3 VCEPSkipped per workflow directive. Details ▾Hide ▴

No further detail was recorded.

PM4 N/ASkipped per workflow directive. Details ▾Hide ▴

No further detail was recorded.

PP4 VCEPThe PTEN VCEP specifies PP4 as 'Not Applicable' because phenotype specificity has been incorporated into the PS4 rule specifications. Details ▾Hide ▴

Sources

cspec ↗

BP1 VCEPThe PTEN VCEP specifies BP1 as 'Not Applicable.' Details ▾Hide ▴

Sources

cspec ↗

BP3 VCEPSkipped per workflow directive. Details ▾Hide ▴

No further detail was recorded.

BP6 VCEPThe PTEN VCEP designates BP6 as 'Not Applicable for this VCEP' per ClinGen SVI VCEP Review Committee recommendation. Additionally, the ClinVar expert panel classification for this variant is Likely Pathogenic (not benign), so BP6 evidence of a benign classification from a reputable source is not available even if the criterion were applied. Details ▾Hide ▴

Evidence considered

VCEP PTEN BP6: Not Applicable per ClinGen SVI VCEP Review Committee
ClinVar EP classification is Likely Pathogenic
not benign

Sources

cspec ↗clinvar ↗

PS5 N/ANot a standard ACMG/AMP criterion in the PTEN VCEP framework. The same-amino-acid-change scenario for this variant is fully adjudicated under PS1. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: PTEN
Transcript: NM_000314.8
Coding (HGVS c.): NM_000314.8:c.106G>C
Protein (HGVS p.): NP_000305.3:p.(Gly36Arg)
GRCh38: chr10:87894051 G>C
GRCh37: chr10:89653808 G>C
ClinVar: 189400
COSMIC: COSV100909550

Gene diagram

Every interpreted variant in PTEN, mapped onto the exon structure of NM_000314.8. Select a row to find it on the plot.

PTENNM_000314.8

Fetching transcript structure from UCSC…

Exons

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Transcript span

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Strand

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Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in PTEN — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 Allele count data not recorded

gnomAD v2.1 Allele count data not recorded

gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -33 bp

0.180

SpliceAI acceptor gainat +13 bp

0.270

SpliceAI donor lossat -33 bp

0.000

SpliceAI donor gainat +58 bp

0.080

Pangolin splice lossmagnitude shown

-0.200

Pangolin splice gain

0.310

Other predictors

REVEL: 0.995
BayesDel: 0.617

How the predictions were used

Evidence considered

REVEL score 0.995 > 0.7 (VCEP threshold)
BayesDel score 0.617 (supports damaging prediction)

Sources

revelbayesdel

Evidence considered

REVEL score 0.995 > 0.5 (BP4 threshold not met)
SpliceAI max delta 0.27 > 0.2 (splicing impact cannot be excluded)

Sources

revelspliceai ↗

Evidence considered

c.106G>C is a missense substitution
not a synonymous or intronic variant

Statement

In silico

SpliceAI predicts possible splice impact for this variant (max delta score = 0.27). REVEL score = 0.995. BayesDel score = 0.616964.

7 paper records listed. 2 cited in the classification.

Cited in the classification

Germline PTEN mutations in three families with Cowden syndrome.

Celebi JT et al. · 2000 Apr

Reports NM_000314.8:c.106G>A (p.Gly36Arg) in a 47-year-old female with Cowden syndrome presenting with trichilemmomas, oral papillomatosis, acral keratosis, uterine fibroids, gastrointestinal polyps, macrocephaly, and bilateral breast carcinoma diagnosed at ages 28 and 31. The recombinant mutant PTEN protein showed 90% loss of phosphatase activity. The variant was confirmed absent in 30 unaffected unrelated individuals.
→ PS1 → PS3 Names this variant
PMID 10772390 ↗
Source detail

the recombinant mutant PTEN protein showed a 90% loss of its phosphatase activity

Location Results, Table 1 (MHS-65-1); Discussion paragraphs 1-2

Context In vitro phosphatase assay using recombinant PTEN protein
A comprehensive functional analysis of PTEN mutations: implications in tumor- and autism-related syndromes.

Rodríguez-Escudero I et al. · 2011 Nov 1

G36R was tested among a panel of 24 PHTS-associated PTEN missense mutations in a yeast in vivo heterologous reconstitution system measuring PIP3 phosphatase activity. Most PHTS-associated mutations, including G36R, generated total or partial loss of function. Global comparison demonstrated that PHTS-associated mutations were significantly more deleterious than ASD/DD-associated mutations (p<0.001).
→ PS3 Names this variant
PMID 21828076 ↗
Source detail

mutations A34D, M35R, G36R, N48K, H61D, Y68D, D92E, H93Y, P96Q, H123D, C124S, G129E, R130G, Y155C, G165E, G165V, S170R, L181P, V217N, P246L, R335L, V343E; L345V and F347L

Location Results, PHTS mutations section; Figure 6A; Supplementary Material Table S1

Context Yeast S. cerevisiae heterologous expression system; p110alpha-CAAX co-expression; GFP-Akt1 membrane localization readout

Other recorded publications

Mutational profile of the PTEN gene in primary human astrocytic tumors and cultivated xenografts.

Mutational profile of PTEN in primary human astrocytic tumors and xenografts. The full text contains only download metadata; no actual article content is available. NM_000314.8:c.106G>C was not identifiable in the available material.
Does not name this variant
PMID 10560660 ↗
Characterizing mutational heterogeneity in a glioblastoma patient with double recurrence.

Characterizes mutational heterogeneity in a glioblastoma patient with double recurrence using ultra-deep sequencing. NM_000314.8:c.106G>C (p.Gly36Arg) was not identified in this paper.
Does not name this variant
PMID 22536362 ↗
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.

Syngal S et al. · 2015

ACG clinical guideline on genetic testing and management of hereditary gastrointestinal cancer syndromes. Cowden syndrome is discussed at the syndrome level. NM_000314.8:c.106G>C was not mentioned in this guideline.
Does not name this variant
PMID 25645574 ↗
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

ACMG/AMP standards and guidelines for the interpretation of sequence variants. This is a methodological guideline that does not discuss specific PTEN variants. NM_000314.8:c.106G>C was not mentioned.
Does not name this variant
PMID 25741868 ↗
American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.

Saslow D et al. · 2007

American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. This is a screening guideline that does not discuss specific PTEN variants. NM_000314.8:c.106G>C was not mentioned.
Does not name this variant
PMID 17392385 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.270 Open source ↗

ClinVar 1 Pathogenic · 1 Uncertain significance Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

OncoKB Captured OncoKB source record Open source ↗

ClinGen CSpec Captured ClinGen CSpec source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Pathogenic (1 clinical laboratory) and as Uncertain significance (1 clinical laboratory) and as Likely pathogenic by Clingen PTEN Variant Curation Expert Panel, Clingen (expert panel). (ClinVarID = 189400)

In silico

SpliceAI predicts possible splice impact for this variant (max delta score = 0.27). REVEL score = 0.995. BayesDel score = 0.616964.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Loss-of-function; curated oncogenicity label: Oncogenic.

Somatic

This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV100909550, n = 1 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.