About TSC1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TSC1 c.2194C>T, p.(His732Tyr)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
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 Not recorded. 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: 0
Benign evidence criteria: 3
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 3
BS1Strong
BS1 · strong
The variant is present in gnomAD v2.1 at AF 0.387% (1093/282512 alleles, 7 homozygotes) and gnomAD v4.1 at AF 0.360% (5806/1612416 alleles, 28 homozygotes). Both overall frequencies exceed the 0.3% BS1 threshold. The presence of 7–28 apparently healthy homozygous individuals in population databases for an autosomal dominant tumor suppressor gene (TSC1) provides strong evidence that this variant is benign. PMID:19918125 independently reported the allele at 0.5% in the normal population and concluded it 'cannot be sufficient to cause TSC or FCD.'
BP4Supporting
BP4 · supporting
Multiple in silico predictors consistently indicate a benign impact. REVEL score is 0.338 (below the 0.5 threshold for pathogenic prediction), BayesDel score is -0.064 (negative, favoring benign), and SpliceAI max delta is 0.09 (below the 0.2 threshold for splicing impact). All three orthogonal computational tools agree on a benign/non-damaging prediction.
BP6Supporting
BP6 · supporting
This variant is classified as Benign in ClinVar by 23 clinical laboratories and as Likely benign by 4 clinical laboratories (ClinVar Variation ID: 5103). The review status is 'criteria provided, single submitter.' The strong clinical consensus — 23 out of 27 classified submissions are 'Benign' — supports a benign interpretation under BP6.
Recorded classification: Likely benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 strong, BP4 supporting benign, BP6 supporting benign; combination = 1 strong benign + 2 supporting benign, which maps to Likely Benign.
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
5,806 / 1,612,416 alleles
gnomAD v4.1: 5,806 / 1,612,416 alleles. Recorded AF 0.00360081. Recorded homozygote count 28.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00386886; MAF= 0.38689%, 1093/282512 alleles, homozygotes = 7) and has highest observed frequency in the European (Finnish) population (AF= 0.0138159; MAF= 1.38159%, 347/25116 alleles, homozygotes = 3); grpmax FAF= 0.00616893.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.002062975027144408, 38/18420 alleles, homozygotes = 0).
SpliceAI score
0.090 maximum delta
Recorded SpliceAI maximum delta score: 0.090. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
27 reported laboratory submissions
23 Benign · 4 Likely benign.
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. TSC1, a scaffold protein, is frequently altered by mutation in bladder cancer.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
6 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV104404438, n = 6 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
27 criteria with recorded statuses: 3 met · 11 not met · 7 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000368.5:c.2194C>T (p.His732Tyr) is a missense variant in TSC1, a gene in which loss-of-function variants cause tuberous sclerosis complex (autosomal dominant).
The variant is present in gnomAD v2.1 at an allele frequency of 0.387% (1093/282512 alleles) with 7 homozygotes, and in gnomAD v4.1 at 0.360% (5806/1612416 alleles) with 28 homozygotes. This frequency exceeds the 0.3% threshold for BS1 (strong benign).
The presence of 28 homozygous individuals in gnomAD v4.1 is incompatible with a highly penetrant autosomal dominant tumor suppressor disorder; homozygous loss of TSC1 function would be expected to cause severe disease.
Multiple in silico predictors support a benign interpretation: REVEL score 0.338 (below 0.5 pathogenic threshold), BayesDel score -0.064 (negative score), and SpliceAI max delta 0.09 (below 0.2 splicing threshold), meeting BP4 (supporting benign).
In ClinVar, 23 clinical laboratories classify this variant as Benign and 4 as Likely benign (Variation ID: 5103), meeting BP6 (supporting benign).
PMID:19918125 (Lugnier et al. 2009) characterized hamartin H732Y in vitro and demonstrated reduced tuberin binding (2.3-fold, p<0.05) and aberrant nuclear localization. However, the paper explicitly reported the allele at 0.5% frequency in the normal population and concluded it 'cannot be sufficient to cause TSC or FCD,' describing it as a low-penetrance predisposing variant at most.
Applying generic ACMG/AMP 2015 combination rules (PMID:25741868): one strong benign criterion (BS1) plus two supporting benign criteria (BP4, BP6) yields a final classification of Likely Benign.
No criteria match.
Met · 3
BS1 StrongThe variant is present in gnomAD v2.1 at AF 0.387% (1093/282512 alleles, 7 homozygotes) and gnomAD v4.1 at AF 0.360% (5806/1612416 alleles, 28 homozygotes). Both overall frequencies exceed the 0.3% BS1 threshold. The presence of 7–28 apparently healthy homozygous individuals in population databases for an autosomal dominant tumor suppressor gene (TSC1) provides strong evidence that this variant is benign. PMID:19918125 independently reported the allele at 0.5% in the normal population and concluded it 'cannot be sufficient to cause TSC or FCD.' Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.387% with 7 homozygotes
- gnomAD v4.1 AF=0.360% with 28 homozygotes
- PMID:19918125 reports 0.5% in normal population and explicitly states variant cannot cause TSC
Sources
BP4 SupportingMultiple in silico predictors consistently indicate a benign impact. REVEL score is 0.338 (below the 0.5 threshold for pathogenic prediction), BayesDel score is -0.064 (negative, favoring benign), and SpliceAI max delta is 0.09 (below the 0.2 threshold for splicing impact). All three orthogonal computational tools agree on a benign/non-damaging prediction. Details ▾Hide ▴
Evidence considered
- REVEL=0.338 (<0.5)
- BayesDel=-0.064 (negative score)
- SpliceAI delta=0.09 (<0.2)
Sources
BP6 SupportingThis variant is classified as Benign in ClinVar by 23 clinical laboratories and as Likely benign by 4 clinical laboratories (ClinVar Variation ID: 5103). The review status is 'criteria provided, single submitter.' The strong clinical consensus — 23 out of 27 classified submissions are 'Benign' — supports a benign interpretation under BP6. Details ▾Hide ▴
Evidence considered
- ClinVar: Benign (23 labs)
- Likely benign (4 labs)
- Variation ID 5103
Sources
Not met · 11 · evaluated, threshold not reached
PS2 One confirmed de novo occurrence reported (PMID:17304050) in a TSC proband with confirmed parental testing, but PS2 requires ≥2 de novo observations for strong evidence. A single de novo case is insufficient to meet PS2, especially given the variant is common in population databases (gnomAD AF 0.37%, 7–28 homozygotes). Details ▾Hide ▴
Evidence considered
- One confirmed de novo case reported in PMID:17304050 per exploratory review
- insufficient to meet threshold
Still missing
- Only a single de novo case identified
- additional independent de novo observations would be needed
PS3 PMID:19918125 (Lugnier et al. 2009) characterized hamartin H732Y in vitro: coimmunoprecipitation assays demonstrated 2.3-fold reduced tuberin binding (p<0.05, n=9 replicates), and the variant showed aberrant nuclear localization in HEK293T cells. However, the paper explicitly states this allele is present in 0.5% of the normal population and 'cannot be sufficient to cause TSC or FCD.' PS3 requires well-established functional studies showing a damaging effect in a disease-relevant context; the in vitro impairment is present but the variant's high population frequency and the authors' own conclusion that it is not disease-causing preclude application of PS3. Details ▾Hide ▴
Evidence considered
- Reduced tuberin binding (2.3-fold
- p<0.05) and aberrant nuclear localization in HEK293T cells
- but the paper concludes this variant is found in normal population and cannot cause TSC
Still missing
- Functional data show partial impairment but paper itself notes the variant is common in unaffected individuals
Sources
PMID:19918125 ↗19918125
PS4 The variant has been observed in TSC patient cohorts (1/325 probands in PMID:17304050; also reported in PMID:15798777), but the prevalence in affected individuals does not significantly exceed the general population frequency of ~0.37% (gnomAD). No formal case-control study with a statistically significant odds ratio has been conducted. Details ▾Hide ▴
Evidence considered
- Observed in 1/325 TSC probands (PMID:17304050)
- variant is present at 0.37% in gnomAD
- so prevalence in cases is not enriched above population background
Still missing
- No formal case-control study comparing variant frequency in affected vs unaffected populations
Sources
PM1 Residue His732 lies outside the well-established TSC1 functional domains. The N-terminal TSC2-binding domain spans amino acids 1–266 and the C-terminal coiled-coil tuberin-binding domain spans amino acids 881–1084 (PMID:9580671). His732 is not in a critical functional domain, a recognized mutational hotspot, or a region where pathogenic missense variants are enriched. Details ▾Hide ▴
Evidence considered
- Residue 732 is outside known TSC2-binding domains (aa 1–266
- 881–1084 per PMID:9580671)
- not in a mutational hotspot
PM2 The variant is present in gnomAD v2.1 at AF 0.00387 (0.387%, 1093/282512 alleles, 7 homozygotes) and in gnomAD v4.1 at AF 0.00360 (0.360%, 5806/1612416 alleles, 28 homozygotes). Both frequencies exceed the 0.1% threshold for PM2. The variant is common, not rare. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.387%
- gnomAD v4.1 AF=0.360%
- both >0.1% threshold
Sources
PM6 One presumed de novo occurrence without confirmation of paternity/maternity was reported (PMID:15798777). However, PM6 requires ≥2 independent assumed de novo events to reach moderate strength, and the variant's high population frequency (gnomAD AF 0.37%) makes a de novo interpretation unreliable. A single presumed de novo in the context of a common population variant does not meet PM6. Details ▾Hide ▴
Evidence considered
- One presumed de novo case without parental confirmation (PMID:15798777)
- insufficient given high population frequency
Still missing
- Insufficient de novo observations
- variant is too common in population for de novo interpretation to be reliable
Sources
PP3 Multiple in silico predictors suggest a benign impact: REVEL score 0.338 (threshold ≥0.5 for pathogenic), BayesDel score -0.064 (threshold >0 for pathogenic), SpliceAI max delta 0.09 (threshold ≥0.2 for splice effect). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL=0.338 (<0.5)
- BayesDel=-0.064 (<0)
- SpliceAI max delta=0.09 (<0.2)
Sources
PP5 ClinVar classification for this variant is Benign (23 clinical laboratories) and Likely benign (4 laboratories); PP5 is applicable only when reputable sources classify the variant as pathogenic. The consensus benign classification precludes PP5. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Benign (23 labs) / Likely benign (4 labs)
- PP5 requires a pathogenic assertion
Sources
BA1 The overall gnomAD allele frequency is 0.37% (v2.1) and 0.36% (v4.1), which is below the 1% BA1 threshold. Although the Finnish subpopulation frequency reaches 1.38% (v2.1) with 3 homozygotes, the grpmax filtering allele frequency (upper bound of 95% CI for the highest subpopulation) is 0.62% (v2.1) and 0.38% (v4.1) — below 1%. Using the conservative grpmax FAF metric, BA1 is not met. However, BS1 is met (see below). Details ▾Hide ▴
Evidence considered
- Overall AF=0.37% (<1%)
- grpmax FAF=0.62% (<1%)
- Finnish raw AF=1.38% noted but does not meet BA1 under conservative grpmax framework
Sources
BS3 No well-established functional studies demonstrate that the H732Y variant has no damaging effect on protein function. The available functional data (PMID:19918125) shows reduced tuberin binding and aberrant nuclear localization — a partially impaired phenotype, not a benign functional result. BS3 requires functional evidence showing no deleterious impact. Details ▾Hide ▴
Evidence considered
- PMID:19918125 shows reduced tuberin binding (2.3-fold
- p<0.05) — not a benign functional result
- no benign functional studies exist
Still missing
- No functional studies demonstrating benign effect are available
Sources
PMID:19918125 ↗19918125
BP1 BP1 is applicable to missense variants in genes where primarily truncating variants cause disease. While TSC1 disease mechanism is loss-of-function, numerous pathogenic missense variants are also well-documented in TSC1. The gene does not have a predominantly truncating pathogenic variant spectrum, so BP1 does not apply. Details ▾Hide ▴
Evidence considered
- TSC1 has both truncating and missense pathogenic variants
- not a predominantly truncating disease mechanism
Not assessed · 7 · no assessment recorded
PS1 No known pathogenic variant resulting in the same amino acid change (His732Tyr) was identified. PS1 requires a previously classified pathogenic variant at the same residue with an identical predicted amino acid consequence. Details ▾Hide ▴
Still missing
- No pathogenic comparator at His732 with the same His→Tyr change is catalogued
PP1 No published cosegregation data are available for this variant in families with multiple affected individuals. Cosegregation with disease in ≥3–4 affected family members would be needed to apply PP1. Details ▾Hide ▴
Still missing
- No family cosegregation studies published for this variant
PP4 PP4 requires detailed patient phenotype information and specificity scoring; insufficient phenotype data are available to assess whether the variant is enriched in patients with a phenotype highly specific for TSC1-related disease. Details ▾Hide ▴
Still missing
- Detailed phenotype data not available for systematic PP4 assessment
BS2 BS2 (observed in a healthy adult individual for a fully penetrant disorder) is superseded by BS1, which provides stronger population-based evidence using allele frequency rather than individual observations. Details ▾Hide ▴
No further detail was recorded.
BS4 No published reports demonstrate lack of segregation of this variant with disease in affected families. The strong population evidence (BS1) provides comparable weight to BS4. Details ▾Hide ▴
Still missing
- No systematic family segregation studies for this variant
BP5 BP5 requires an alternate molecular basis for disease in a case where the variant is observed. No such data were identified for this case; the strong population evidence (BS1) is the primary benign criterion. Details ▾Hide ▴
No further detail was recorded.
PS5 No alternate pathogenic variant at the same nucleotide position (c.2194) has been identified and classified as pathogenic. PS5 requires a different nucleotide change at the same position with an established pathogenic classification. Details ▾Hide ▴
Still missing
- No alternate pathogenic nucleotide change at c.2194 is catalogued
Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000368.5:c.2194C>T is a missense variant (p.His732Tyr); PVS1 is applicable only to null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, single/multi-exon deletions). This variant does not fall into any null-variant bucket. Details ▾Hide ▴
Evidence considered
- Missense substitution at codon 732
- not a null variant
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PM5 N/ANo same-residue comparator variants with a different pathogenic amino acid change could be confirmed by automated candidate harvesting. Classic PM5 semantics could not be established. Details ▾Hide ▴
Evidence considered
- No qualifying same-residue (His732) comparator variants identified
Sources
pm5_candidates
PP2 N/APP2 applies to genes where missense variants are a common mechanism of disease and the gene has a low rate of benign missense variation (high missense Z-score). TSC1 has a missense Z-score that does not meet the threshold for PP2, and the variant is common in population databases. Details ▾Hide ▴
Evidence considered
- TSC1 missense constraint metrics do not support PP2 applicability
BP2 N/ABP2 applies to variants observed in trans with a pathogenic variant in a fully penetrant recessive disorder. TSC1-related tuberous sclerosis complex is an autosomal dominant condition; BP2 is not applicable. Details ▾Hide ▴
No further detail was recorded.
BP3 N/ASkipped: in-frame deletions/insertions in repetitive regions are not applicable to this missense substitution variant. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies to synonymous (silent) variants predicted not to affect splicing. c.2194C>T is a missense variant (p.His732Tyr), not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- TSC1
- Transcript
- NM_000368.5
- Coding (HGVS c.)
- NM_000368.5:c.2194C>T
- Protein (HGVS p.)
- NP_000359.1:p.(His732Tyr)
- GRCh38
- chr9:132903665 G>A
- GRCh37
- chr9:135779052 G>A
- ClinVar
- 1719479, 48942, 5103
- COSMIC
- COSV104404438
Gene diagram
Every interpreted variant in TSC1, mapped onto the exon structure of NM_000368.5. Select a row to find it on the plot.
TSC1NM_000368.5
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 TSC1
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
5,806 / 1,612,416 alleles
AF 0.0036 · 28 homozygotes · FAF 0.00382
gnomAD v2.1
1,093 / 282,512 alleles
AF 0.00387 · 7 homozygotes · FAF 0.00617
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.0036 · 5806 / 1,612,416 alleles · 28 hom · FAF 0.0038
| European (Finnish)896 / 64,030 | 0.01411 hom |
| European (non-Finnish)4619 / 1,179,952 | 0.003916 hom |
| Remaining individuals183 / 62,348 | 0.00291 hom |
| Admixed American66 / 60,028 | 0.0011 |
| African/African American40 / 74,996 | 0.00053 |
| Ashkenazi Jewish1 / 29,604 | 3.4e-05 |
| South Asian1 / 91,000 | 1.1e-05 |
0 alternate alleles recorded in 3 other groups: Amish, East Asian, Middle Eastern.
gnomAD v2.1
AF 0.0039 · 1093 / 282,512 alleles · 7 hom · FAF 0.0062
| European (Finnish)347 / 25,116 | 0.0143 hom |
| European (non-Finnish)650 / 128,862 | 0.0054 hom |
| Remaining individuals32 / 7,210 | 0.0044 |
| Admixed American43 / 35,436 | 0.0012 |
| African/African American21 / 24,964 | 0.00084 |
0 alternate alleles recorded in 3 other groups: Ashkenazi Jewish, East Asian, South Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00360081; MAF= 0.36008%, 5806/1612416 alleles, homozygotes = 28) and has highest observed frequency in the European (Finnish) population (AF= 0.0139934; MAF= 1.39934%, 896/64030 alleles, homozygotes = 11); grpmax FAF= 0.00382016.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00386886; MAF= 0.38689%, 1093/282512 alleles, homozygotes = 7) and has highest observed frequency in the European (Finnish) population (AF= 0.0138159; MAF= 1.38159%, 347/25116 alleles, homozygotes = 3); grpmax FAF= 0.00616893.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.002062975027144408, 38/18420 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.338
- BayesDel
- -0.064
How the predictions were used
BP4 SupportingMultiple in silico predictors consistently indicate a benign impact. REVEL score is 0.338 (below the 0.5 threshold for pathogenic prediction), BayesDel score is -0.064 (negative, favoring benign), and SpliceAI max delta is 0.09 (below the 0.2 threshold for splicing impact). All three orthogonal computational tools agree on a benign/non-damaging prediction. Details ▾Hide ▴
Evidence considered
- REVEL=0.338 (<0.5)
- BayesDel=-0.064 (negative score)
- SpliceAI delta=0.09 (<0.2)
Sources
PP3 Multiple in silico predictors suggest a benign impact: REVEL score 0.338 (threshold ≥0.5 for pathogenic), BayesDel score -0.064 (threshold >0 for pathogenic), SpliceAI max delta 0.09 (threshold ≥0.2 for splice effect). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL=0.338 (<0.5)
- BayesDel=-0.064 (<0)
- SpliceAI max delta=0.09 (<0.2)
Sources
BP7 N/ABP7 applies to synonymous (silent) variants predicted not to affect splicing. c.2194C>T is a missense variant (p.His732Tyr), not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.09). REVEL score = 0.338. BayesDel score = -0.0641334.
10 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 10227394 ↗Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.van Slegtenhorst M et al. · 1999No paper-specific finding is recorded.
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PMID 19918125 ↗Hamartin variants that are frequent in focal dysplasias and cortical tubers have reduced tuberin binding and aberrant subcellular distribution in vitro.Lugnier C et al. · 2009No paper-specific finding is recorded.
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PMID 21309039 ↗Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex.No paper-specific finding is recorded.
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PMID 23514105 ↗Lack of association of rare functional variants in TSC1/TSC2 genes with autism spectrum disorder.No paper-specific finding is recorded.
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PMID 24033266 ↗A systematic approach to assessing the clinical significance of genetic variants.No paper-specific finding is recorded.
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PMID 25741868 ↗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.No paper-specific finding is recorded.
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
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PMID 27425891 ↗Minute amounts of hamartin wildtype rescue the emergence of tuber-like lesions in conditional Tsc1 ablated mice.Robens BK et al. · 2016No paper-specific finding is recorded.
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PMID 18414213 ↗ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
5,806 / 1,612,416 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.090
Open source ↗
ClinVar
23 Benign · 4 Likely benign
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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/5103/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/9-135779052-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr9-132903665-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/9-132903665-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000368.5%3Ac.2194…
- OncoKB ↗www.oncokb.org/gene/TSC1/H732Y
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=122157835
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00360081; MAF= 0.36008%, 5806/1612416 alleles, homozygotes = 28) and has highest observed frequency in the European (Finnish) population (AF= 0.0139934; MAF= 1.39934%, 896/64030 alleles, homozygotes = 11); grpmax FAF= 0.00382016.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00386886; MAF= 0.38689%, 1093/282512 alleles, homozygotes = 7) and has highest observed frequency in the European (Finnish) population (AF= 0.0138159; MAF= 1.38159%, 347/25116 alleles, homozygotes = 3); grpmax FAF= 0.00616893.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.002062975027144408, 38/18420 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Benign (23 clinical laboratories) and as Likely benign (4 clinical laboratories). (ClinVarID = 5103)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.09). REVEL score = 0.338. BayesDel score = -0.0641334.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. TSC1, a scaffold protein, is frequently altered by mutation in bladder cancer.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV104404438, n = 6 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.