About MLH1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MLH1 c.1094G>A, p.(Ser365Asn)
Classification
Not classified
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. Select a step to read what it means.
Not classified yet.Select a step to read what it means.
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 ClinGen MLH1 VCEP v2.0.0. 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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_000249.4:c.1094G>A is absent from gnomAD v4.1 (and v2.1), satisfying the VCEP PM2_Supporting rule: absent/extremely rare allele frequency <0.00002 (<1 in 50,000 alleles) in the gnomAD v4 dataset.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Per the MLH1 VCEP v2.0.0, BP4_Supporting is met when the HCI prior probability of pathogenicity is <0.11 for missense variants. The HCI prior for c.1094G>A (p.Ser365N) is 0.0025, which is well below the threshold. Additionally, REVEL score is 0.321 and BayesDel score is -0.220172, both consistent with a benign in silico prediction profile.
Recorded classification: Not classified
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MLH1 Version 2.0.0 v2.0.0 criteria-combination framework: matched Rule31 (Benign.Supporting >=1 + Pathogenic.Supporting >=1) with applied criteria: PM2 supporting, BP4 supporting benign; maps to Uncertain Significance - Conflicting Evidence.
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.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
4 Uncertain significance.
Context only
ClinVar ↗
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. MLH1, a DNA mismatch repair protein, is recurrently altered by deletion and mutation in various cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen MLH1 VCEP v2.0.0, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 5 not met · 9 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000249.4:c.1094G>A (p.Ser365Asn) is a missense variant in exon 12 of MLH1, absent from gnomAD v4.1 and v2.1 (PM2_Supporting per VCEP v2.0.0).
In silico predictors strongly favor a benign effect: HCI prior probability is 0.0025 (BP4_Supporting per VCEP, threshold <0.11), REVEL score is 0.321, and BayesDel score is -0.220172.
SpliceAI predicts no splicing impact (max delta score 0.01), confirming the variant does not create a cryptic splice site.
The InSiGHT Locus-Specific Database (Thompson et al. 2013, PMID:22949387) classifies this variant as Class 5 (Pathogenic) based on a multifactorial likelihood model incorporating yeast-based MMR functional defect data and co-segregation in multiple families, but the quantitative calibrated functional odds and segregation likelihood ratios required for VCEP PS3 and PP1 strength assignment were not available in the case materials.
ClinVar reports this variant as Uncertain Significance (4 clinical laboratories, criteria provided single submitter, ClinVar ID 1790197).
No tumor pathology data (MSI status, MMR IHC, BRAF V600E, MLH1 methylation) was available to assess PP4 or BP5.
Several criteria designated as Not Applicable by the VCEP were not assessed: PVS1 (missense, not null), PS4, PM1, PM6, PP2, PP5, BP1, BP2, BP6, BP7.
No criteria match.
Met · 2
PM2 SupportingNM_000249.4:c.1094G>A is absent from gnomAD v4.1 (and v2.1), satisfying the VCEP PM2_Supporting rule: absent/extremely rare allele frequency <0.00002 (<1 in 50,000 alleles) in the gnomAD v4 dataset. Details ▾Hide ▴
Evidence considered
- Variant is absent from gnomAD v4.1 (0 alleles). Also absent from gnomAD v2.1. Meets VCEP PM2_Supporting threshold (<0.00002).
Sources
BP4 SupportingPer the MLH1 VCEP v2.0.0, BP4_Supporting is met when the HCI prior probability of pathogenicity is <0.11 for missense variants. The HCI prior for c.1094G>A (p.Ser365N) is 0.0025, which is well below the threshold. Additionally, REVEL score is 0.321 and BayesDel score is -0.220172, both consistent with a benign in silico prediction profile. Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.0025 (<0.11 threshold for BP4_Supporting). REVEL = 0.321 (below typical pathogenic threshold). BayesDel = -0.220 (negative score consistent with benign).
Sources
Not met · 5 · evaluated, threshold not reached
PP3 Per the MLH1 VCEP v2.0.0, PP3 for missense variants is assessed by HCI prior probability: >0.81 = PP3_Moderate, >0.68 and ≤0.81 = PP3_Supporting. The HCI prior for c.1094G>A (p.Ser365N) is 0.0025, well below both thresholds. SpliceAI delta score is 0.01, also below the non-canonical splice threshold of 0.2. Neither criterion for PP3 is met. Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.0025 (threshold for PP3_Supporting is >0.68). SpliceAI max delta = 0.01 (threshold for PP3_Supporting via splicing is ≥0.2). Neither threshold is met.
Sources
BA1 Per the MLH1 VCEP v2.0.0, BA1 requires gnomAD v4 Grpmax filtering allele frequency ≥0.001 (0.1%) with exclusion as a founder pathogenic variant. The variant is absent from gnomAD v4.1 (0 alleles), far below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- Variant is absent from gnomAD v4.1. BA1 requires AF ≥0.001.
Sources
BS1 Per the MLH1 VCEP v2.0.0, BS1 requires gnomAD v4 Grpmax filtering allele frequency ≥0.0001 and <0.001 (0.01-0.1%) with exclusion as a founder pathogenic variant. The variant is absent from gnomAD v4.1, so BS1 is not met. Details ▾Hide ▴
Evidence considered
- Variant is absent from gnomAD v4.1. BS1 requires AF ≥0.0001 and <0.001.
Sources
BS3 BS3 requires calibrated functional assays showing functional odds for pathogenicity ≤0.05 (Strong) or >0.05 and ≤0.48 (Supporting), or proficient function per the MMR functional assay flowchart. The available functional evidence (InSiGHT database, PMID:22949387) indicates a damaging effect in a yeast-based MMR assay, which is inconsistent with normal/proficient function. The VCEP Functional-assay-SVI-documentation-MMR.xlsx lists calibrated assays but does not contain variant-specific data for c.1094G>A. No evidence of normal MMR function for this variant was identified. Details ▾Hide ▴
Evidence considered
- InSiGHT database reports damaging functional effect (yeast MMR assay). VCEP calibrated functional assay documentation does not contain c.1094G>A. No evidence of proficient/normal MMR function.
Sources
hci_priorvcep_functional_assay_svi_documentation_mmr
BS4 BS4 requires lack of co-segregation with disease in pedigrees (combined Bayes Likelihood Ratio <0.05 for Strong, >0.05 and ≤0.48 for Supporting). The InSiGHT Locus-Specific Database reports co-segregation of this variant with Lynch syndrome-spectrum cancers, which is the opposite of what BS4 requires. No evidence of non-segregation was identified. Details ▾Hide ▴
Evidence considered
- InSiGHT database reports co-segregation with disease
- inconsistent with BS4. No evidence of non-segregation identified.
Sources
hci_prior
Not assessed · 9 · no assessment recorded
PS1 PS1 requires a different nucleotide change encoding the same amino acid (Ser365Asn) previously established as Pathogenic by this VCEP. No such comparator variant was identified in the VCEP pilot variants spreadsheet or in the available evidence. The InSiGHT Locus-Specific Database classification of this variant itself is Class 5 (Pathogenic), but that does not constitute a comparator for PS1. Details ▾Hide ▴
Still missing
- No alternate nucleotide change at codon 365 encoding Ser365Asn classified as Pathogenic by the VCEP was identified.
PS2 No de novo occurrence reports were identified for NM_000249.4:c.1094G>A. The exploratory literature search found no evidence of de novo status in Lynch syndrome or constitutional mismatch repair deficiency (CMMRD). De novo events in adult-onset cancer syndromes are rarely documented. Details ▾Hide ▴
Still missing
- No de novo reports identified for this variant.
PS3 The InSiGHT Locus-Specific Database (Thompson et al. 2013, PMID:22949387) classifies c.1094G>A (p.Ser365Asn) as Class 5 (Pathogenic) based on a multifactorial likelihood model incorporating functional data (yeast-based MMR defect assay). However, the calibrated functional odds ratio required by the VCEP PS3 strength table (Strong: >18.7; Moderate: >4.3 and ≤18.7; Supporting: >2.08 and ≤4.3) was not available. The VCEP Functional-assay-SVI-documentation-MMR.xlsx does not contain variant-specific entries for c.1094G>A, and the calibrated assays listed therein (Drost 2018/2020, Jia/Scott 2021/2022, Rath 2022) do not include this variant. Full text of PMID:22949387 was not available in the case materials for direct verification of the functional data. Details ▾Hide ▴
Evidence considered
- InSiGHT Locus-Specific Database (PMID:22949387) classifies this variant as Class 5 (Pathogenic) with yeast-based MMR functional defect data
- but calibrated functional odds for VCEP PS3 are not available.
Still missing
- Calibrated functional odds ratio from a VCEP-approved assay (Drost
- Jia/Scott
- or Rath) is needed to assign PS3 strength.
- Full text of PMID:22949387 needed to verify functional assay details and quantitative MMR efficiency values.
Sources
hci_prior
PM5 PM5 requires a different missense change at the same amino acid residue (Ser365) previously classified as Pathogenic or Likely Pathogenic by this VCEP. The pm5_candidates search identified no same-residue comparator variants in ClinVar meeting VCEP Pathogenic/Likely Pathogenic criteria. Without an established pathogenic comparator at codon 365, PM5 cannot be applied. Details ▾Hide ▴
Evidence considered
- No same-residue missense comparator at codon 365 classified as Pathogenic or Likely Pathogenic by the VCEP was identified.
Still missing
- No VCEP-classified pathogenic missense comparator at Ser365 was found.
PP1 The InSiGHT Locus-Specific Database (PMID:22949387) reports co-segregation of c.1094G>A with Lynch syndrome-spectrum cancers in multiple families, contributing to its Class 5 (Pathogenic) classification. However, the specific Bayes Likelihood Ratio required for VCEP PP1 strength assignment (Strong: >18.7 in ≥2 families; Moderate: >4.3 and ≤18.7; Supporting: >2.08 and ≤4.3) was not available in the case materials. The number of meioses, family structures, and LOD scores are recorded in the InSiGHT database but were not retrieved. Details ▾Hide ▴
Evidence considered
- InSiGHT database (PMID:22949387) reports co-segregation in multiple families
- but quantitative Bayes Likelihood Ratio for VCEP PP1 strength assignment is not available.
Still missing
- Bayes Likelihood Ratio from segregation analysis needed for PP1 strength assignment.
- Number of meioses and family structures from InSiGHT database needed.
Sources
hci_prior
PP4 The VCEP PP4 criterion requires MSI-H colorectal or endometrial tumors with loss of MMR protein expression consistent with the variant location, with MLH1 promoter methylation excluded. No tumor pathology data (MSI status, IHC for MMR proteins, BRAF V600E, or MLH1 methylation) was available for this variant in the case materials. Details ▾Hide ▴
Still missing
- Tumor MSI status and MMR IHC data not available.
- BRAF V600E and MLH1 promoter methylation status not available for any observed tumors.
BS2 BS2 requires co-occurrence in trans with a known pathogenic MLH1 variant in a patient with colorectal cancer after age 45 (or other LS cancer above median age of onset) without clinical manifestations of CMMRD. No such co-occurrence data was identified for this variant. Details ▾Hide ▴
Still missing
- No trans co-occurrence data with a pathogenic MLH1 variant identified.
BP5 BP5 requires specific tumor data: ≥4 MSS tumors with no loss of MMR expression (Strong), or 2-3 such tumors (Supporting), or BRAF V600E/MLH1 methylation in MSI-H tumors. No tumor pathology data was available for this variant in the case materials. Details ▾Hide ▴
Still missing
- Tumor MSS/MSI status
- MMR IHC
- BRAF V600E
- and MLH1 methylation data not available for any tumors carrying this variant.
PS5 PS5 (reputable source reports variant as pathogenic) is not defined in the InSiGHT/ClinGen MLH1 VCEP v2.0.0 specification. The equivalent criterion PP5 is explicitly listed as Not Applicable by the VCEP. Under generic ACMG/AMP 2015, PS5 would require a reputable source recently reporting the variant as pathogenic with evidence not available to the laboratory for independent evaluation. The InSiGHT Locus-Specific Database (PMID:22949387) classifies this variant as Class 5 (Pathogenic), but this classification predates the VCEP framework and relies on the same underlying evidence being adjudicated here. Details ▾Hide ▴
Still missing
- VCEP does not define PS5
- generic PS5 requires evaluation of whether a reputable source classification can be adopted.
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants under the InSiGHT/ClinGen MLH1 VCEP v2.0.0. NM_000249.4:c.1094G>A is a missense substitution (p.Ser365Asn) in exon 12. SpliceAI predicts no splicing impact (max delta score 0.01), and the variant does not fall into any PVS1-eligible bucket (nonsense, frameshift, canonical ±1/2 splice, initiation codon, or confirmed splicing aberration). Details ▾Hide ▴
Evidence considered
- Missense variant p.Ser365Asn does not introduce a premature termination codon
- SpliceAI max delta 0.01 confirms no cryptic splice effect.
Sources
PS4 VCEPPS4 is listed as Not Applicable under the InSiGHT/ClinGen MLH1 VCEP v2.0.0 specifications. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
PM1 VCEPPM1 is listed as Not Applicable under the InSiGHT/ClinGen MLH1 VCEP v2.0.0 specifications. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
PM6 VCEPPM6 is listed as Not Applicable under the InSiGHT/ClinGen MLH1 VCEP v2.0.0 specifications. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
PP2 VCEPPP2 is listed as Not Applicable under the InSiGHT/ClinGen MLH1 VCEP v2.0.0 specifications. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
PP5 VCEPPP5 is listed as Not Applicable under the InSiGHT/ClinGen MLH1 VCEP v2.0.0 specifications. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP1 VCEPBP1 is listed as Not Applicable under the InSiGHT/ClinGen MLH1 VCEP v2.0.0 specifications. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP2 VCEPBP2 is listed as Not Applicable under the InSiGHT/ClinGen MLH1 VCEP v2.0.0 specifications. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP6 VCEPBP6 is listed as Not Applicable under the InSiGHT/ClinGen MLH1 VCEP v2.0.0 specifications. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP7 N/ABP7 applies only to synonymous (silent) or intronic variants at or beyond positions -21/+7 (5'/3' exonic). NM_000249.4:c.1094G>A is a missense variant (p.Ser365Asn) and is therefore not eligible for BP7. Details ▾Hide ▴
Evidence considered
- Variant is missense (p.Ser365Asn)
- not synonymous or intronic. BP7 is not applicable.
Sources
Identifiers
- Gene
- MLH1
- Transcript
- NM_000249.4
- Coding (HGVS c.)
- NM_000249.4:c.1094G>A
- Protein (HGVS p.)
- NP_000240.1:p.(Ser365Asn)
- GRCh38
- chr3:37025692 G>A
- GRCh37
- chr3:37067183 G>A
- ClinVar
- 1790197, 916260
Gene diagram
Every interpreted variant in MLH1, mapped onto the exon structure of NM_000249.4. Select a row to find it on the plot.
MLH1NM_000249.4
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 MLH1
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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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.321
- BayesDel
- -0.220
How the predictions were used
BP4 SupportingPer the MLH1 VCEP v2.0.0, BP4_Supporting is met when the HCI prior probability of pathogenicity is <0.11 for missense variants. The HCI prior for c.1094G>A (p.Ser365N) is 0.0025, which is well below the threshold. Additionally, REVEL score is 0.321 and BayesDel score is -0.220172, both consistent with a benign in silico prediction profile. Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.0025 (<0.11 threshold for BP4_Supporting). REVEL = 0.321 (below typical pathogenic threshold). BayesDel = -0.220 (negative score consistent with benign).
Sources
PP3 Per the MLH1 VCEP v2.0.0, PP3 for missense variants is assessed by HCI prior probability: >0.81 = PP3_Moderate, >0.68 and ≤0.81 = PP3_Supporting. The HCI prior for c.1094G>A (p.Ser365N) is 0.0025, well below both thresholds. SpliceAI delta score is 0.01, also below the non-canonical splice threshold of 0.2. Neither criterion for PP3 is met. Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.0025 (threshold for PP3_Supporting is >0.68). SpliceAI max delta = 0.01 (threshold for PP3_Supporting via splicing is ≥0.2). Neither threshold is met.
Sources
BP7 N/ABP7 applies only to synonymous (silent) or intronic variants at or beyond positions -21/+7 (5'/3' exonic). NM_000249.4:c.1094G>A is a missense variant (p.Ser365Asn) and is therefore not eligible for BP7. Details ▾Hide ▴
Evidence considered
- Variant is missense (p.Ser365Asn)
- not synonymous or intronic. BP7 is not applicable.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.321. BayesDel score = -0.220172. HCI prior probability for pathogenicity = 0.0025. Custom PP2 score = 0.007.
9 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 15662714 ↗Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry.Ponti G et al. · 2005No paper-specific finding is recorded.
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PMID 25070057 ↗Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer.No paper-specific finding is recorded.
-
PMID 25645574 ↗ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.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 11598466 ↗Practice parameters for the identification and testing of patients at risk for dominantly inherited colorectal cancer--supporting documentation.Church J et al. · 2001No paper-specific finding is recorded.
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004No paper-specific finding is recorded.
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PMID 20065170 ↗American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility.Robson ME et al. · 2010No paper-specific finding is recorded.
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PMID 20301390 ↗Lynch Syndrome.Adam MP et al. · 1993No 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
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
4 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
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1564688410
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/1790197/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/3-37067183-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr3-37025692-G-A?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000249.4%3Ac.1094…
- OncoKB ↗www.oncokb.org/gene/MLH1/S365N
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MLH1+c.1094G%3EA
- 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
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories). (ClinVarID = 1790197)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.321. BayesDel score = -0.220172. HCI prior probability for pathogenicity = 0.0025. Custom PP2 score = 0.007.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MLH1, a DNA mismatch repair protein, is recurrently altered by deletion and mutation in various cancer types.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.