About MLH1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MLH1 c.1738G>A, p.(Ala580Thr)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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. 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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PM2Supporting
PM2 · supporting
The variant is extremely rare in gnomAD v4.1 with a grpmax filtering allele frequency of 2.8e-07 (2/1,614,160 alleles, 0 homozygotes), which is well below the VCEP PM2_Supporting threshold of <0.00002 (<1 in 50,000 alleles). Absent from gnomAD v2.1.
PP3Supporting
PP3 · supporting
The HCI prior probability for pathogenicity for p.Ala580Thr is 0.8146, which falls in the PP3_Supporting range (>0.68 and ≤0.81) per the InSiGHT VCEP v2.0 specification. SpliceAI predicts no splicing impact (max delta score 0.00), so the splice-based PP3 rule does not apply. REVEL score is 0.703 and BayesDel score is 0.291.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MLH1 Version 2.0 v2.0 criteria-combination framework was evaluated deterministically with applied criteria: PM2 supporting, PP3 supporting; no rule matched the adjudicated criteria.
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
2 / 1,614,160 alleles
gnomAD v4.1: 2 / 1,614,160 alleles. Recorded AF 1.23903e-06. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
6 reported laboratory submissions
4 Uncertain significance · 1 Uncertain Significance · 1 Likely benign. ClinVar API review status: criteria provided, conflicting classifications.
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
2 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV51614640, n = 2 times).
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, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 13 not met · 0 not assessed · 14 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000249.3:c.1738G>A (p.Ala580Thr) is a missense variant in MLH1 exon 16. It is extremely rare in population databases (gnomAD v4.1 grpmax FAF = 2.8e-07), meeting PM2_Supporting per the InSiGHT VCEP v2.0 specification.
In silico analysis yields an HCI prior probability of 0.8146, which falls in the PP3_Supporting range (>0.68 and ≤0.81) per the InSiGHT VCEP v2.0 specification. SpliceAI predicts no splicing impact (max delta score = 0.00). REVEL score is 0.703.
No variant-specific functional data, co-segregation data, tumor phenotype data, or de novo observations were identified in the reviewed literature or ClinVar submissions. ClinVar reports this variant as Uncertain Significance (6 submissions; review status: criteria provided, single submitter).
Under the InSiGHT VCEP v2.0 framework, the only criteria met are PM2_Supporting and PP3_Supporting. Multiple criteria are designated as Not Applicable per the VCEP specification (PS4, PM1, PM6, PP2, PP5, BP1, BP2, BP6, PM4) or are not applicable to a missense substitution (PVS1, BP3, BP7). No benign criteria are met. With only two supporting pathogenic criteria and no moderate, strong, or very strong criteria met, the variant remains as Uncertain Significance per the VCEP combination rules.
No criteria match.
Met · 2
PM2 SupportingThe variant is extremely rare in gnomAD v4.1 with a grpmax filtering allele frequency of 2.8e-07 (2/1,614,160 alleles, 0 homozygotes), which is well below the VCEP PM2_Supporting threshold of <0.00002 (<1 in 50,000 alleles). Absent from gnomAD v2.1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 2.8e-07
- well below the VCEP threshold of 0.00002.
- Absent from gnomAD v2.1.
Sources
PP3 SupportingThe HCI prior probability for pathogenicity for p.Ala580Thr is 0.8146, which falls in the PP3_Supporting range (>0.68 and ≤0.81) per the InSiGHT VCEP v2.0 specification. SpliceAI predicts no splicing impact (max delta score 0.00), so the splice-based PP3 rule does not apply. REVEL score is 0.703 and BayesDel score is 0.291. Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.8146
- meeting VCEP PP3_Supporting threshold (>0.68
- ≤0.81).
- SpliceAI max delta = 0.00
- no predicted splice impact.
- REVEL = 0.703.
Sources
Not met · 13 · evaluated, threshold not reached
PS1 No evidence that a different underlying nucleotide change producing the same amino acid substitution (p.Ala580Thr) has been classified as Pathogenic or Likely Pathogenic by this VCEP. No such variant was identified in the VCEP pilot variants database or in the reviewed literature. Details ▾Hide ▴
Evidence considered
- No alternate nucleotide change producing p.Ala580Thr is classified as P/LP by the InSiGHT VCEP.
Still missing
- No alternate nucleotide at c.1738 creating A580T was found in ClinVar or VCEP pilot variants.
Sources
PS2 No de novo occurrence data were identified for NM_000249.3:c.1738G>A in the reviewed literature or ClinVar submissions. The VCEP PS2 rule requires de novo points from confirmed parentage testing. Details ▾Hide ▴
PS3 No variant-specific functional data were identified for p.Ala580Thr (NM_000249.3:c.1738G>A) in the reviewed literature, the VCEP calibrated functional assay documentation, or OncoKB. The variant is not listed in the VCEP pilot variants spreadsheet with any PS3 or BS3 functional code assignment. Details ▾Hide ▴
Evidence considered
- OncoKB reports Unknown Oncogenic Effect with no variant-specific functional evidence.
- VCEP functional assay spreadsheet lists calibrated MMR assays but does not assign any PS3/BS3 code for p.Ala580Thr.
- VCEP pilot variants spreadsheet does not include this variant.
Still missing
- No calibrated functional assay data available for p.Ala580Thr.
Sources
PM5 No different missense change at amino acid residue 580 was identified that has been classified as Pathogenic or Likely Pathogenic by this VCEP. The VCEP pilot variants spreadsheet does not list any codon 580 comparator. PM5 also requires PP3 to be supporting; although PP3_Supporting is met (HCI prior 0.8146), the absence of a qualifying comparator variant precludes PM5 application. Details ▾Hide ▴
Evidence considered
- No VCEP-classified P/LP missense variant at codon 580 identified as comparator.
Still missing
- No same-residue comparator variant classified as P/LP by InSiGHT VCEP.
Sources
cspec ↗pm5_candidates
PP1 No co-segregation data were identified for this variant in the reviewed literature or ClinVar submissions. The VCEP PP1 rule requires Bayes Likelihood Ratio calculation from pedigrees. Details ▾Hide ▴
PP4 No tumor data (MSI status, MMR protein expression by IHC) were identified for patients carrying NM_000249.3:c.1738G>A in the reviewed literature or ClinVar submissions. The VCEP PP4 rule requires one or more CRC/endometrial MSI-H tumors with loss of MMR protein expression consistent with the variant location. Details ▾Hide ▴
BA1 The gnomAD v4.1 grpmax filtering allele frequency is 2.8e-07, which is far below the VCEP BA1 threshold of ≥0.001 (0.1%). The variant is extremely rare and does not meet the stand-alone benign allele frequency criterion. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 2.8e-07
- well below BA1 threshold of 0.001.
Sources
BS1 The gnomAD v4.1 grpmax filtering allele frequency is 2.8e-07, which is below the VCEP BS1 threshold of ≥0.0001 (0.01%). The variant is too rare to satisfy BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 2.8e-07
- below BS1 threshold of 0.0001.
Sources
BS2 No observation of co-occurrence in trans with a known pathogenic MLH1 variant was identified in the reviewed literature or ClinVar submissions. The VCEP BS2 rule requires documented trans co-occurrence with a known pathogenic variant in a CRC patient after age 45 without CMMRD features. Details ▾Hide ▴
BS3 No functional data demonstrating a benign effect for p.Ala580Thr were identified in the reviewed literature, the VCEP calibrated functional assay documentation, or OncoKB. The variant is not listed in the VCEP pilot variants spreadsheet with any BS3 code assignment. Details ▾Hide ▴
BS4 No lack of co-segregation data were identified for this variant. The VCEP BS4 rule requires Bayes Likelihood Ratio calculation from pedigrees showing absence of segregation with disease. Details ▾Hide ▴
Evidence considered
- No co-segregation or non-segregation data available.
Still missing
- No pedigree data available for BS4 evaluation.
Sources
BP4 The HCI prior probability for pathogenicity for p.Ala580Thr is 0.8146, which is well above the VCEP BP4_Supporting threshold of <0.11. REVEL score is 0.703 and BayesDel score is 0.291, which do not suggest a benign in silico profile. SpliceAI predicts no splice impact (delta 0.00), but the BP4 splice rule applies only to intronic and synonymous variants, not missense. Details ▾Hide ▴
Evidence considered
- HCI prior = 0.8146
- far above BP4 threshold of <0.11.
- REVEL = 0.703
- in the intermediate range.
- SpliceAI delta = 0.00
- but BP4 splice rule is for intronic/synonymous variants only.
Sources
BP5 No tumor data demonstrating MSS status or retained MMR protein expression were identified for patients carrying this variant. The VCEP BP5 rule requires multiple tumors with MSS and/or no loss of MMR protein expression, or BRAF V600E/MLH1 methylation with MSI-H. Details ▾Hide ▴
Evidence considered
- No tumor phenotype data available to support benign interpretation.
Still missing
- No tumor data available for BP5 evaluation.
Sources
Not applicable · 14· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants. NM_000249.3:c.1738G>A is a missense substitution (p.Ala580Thr) and does not fall into any PVS1 null-variant category (nonsense, frameshift, canonical splice, initiation codon, or large deletion). The VCEP PVS1 rules are restricted to null variants and do not apply to missense changes. Details ▾Hide ▴
Evidence considered
- Missense variant p.Ala580Thr is not a null variant
- PVS1 is restricted to nonsense
- frameshift
- canonical splice
- and initiation codon variants per ClinGen InSiGHT VCEP v2.0.
Sources
PS4 VCEPPS4 is designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications for MLH1 Version 2.0. Details ▾Hide ▴
PM1 VCEPPM1 is designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications for MLH1 Version 2.0. Details ▾Hide ▴
PM3 N/APM3 was designated for skip in the case instructions; not assessed. Details ▾Hide ▴
Evidence considered
- Skipped per case instructions.
PM4 VCEPPM4 is designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications for MLH1 Version 2.0. Details ▾Hide ▴
PM6 VCEPPM6 is designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications for MLH1 Version 2.0. Details ▾Hide ▴
PP2 VCEPPP2 is designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications for MLH1 Version 2.0. Details ▾Hide ▴
PP5 VCEPPP5 is designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications for MLH1 Version 2.0. Details ▾Hide ▴
BP1 VCEPBP1 is designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications for MLH1 Version 2.0. Details ▾Hide ▴
BP2 VCEPBP2 is designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications for MLH1 Version 2.0. Details ▾Hide ▴
BP3 VCEPBP3 does not apply to substitution variants. NM_000249.3:c.1738G>A is a single nucleotide substitution, not an in-frame indel. Details ▾Hide ▴
Evidence considered
- Substitution variant
- BP3 is restricted to in-frame deletions/insertions.
BP6 VCEPBP6 is designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications for MLH1 Version 2.0. 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. NM_000249.3:c.1738G>A is a missense variant (p.Ala580Thr) in exon 16 and does not qualify for BP7. Details ▾Hide ▴
Evidence considered
- Missense substitution
- BP7 is restricted to synonymous and intronic variants.
Sources
PS5 N/APS5 is not defined in the ClinGen InSiGHT VCEP v2.0 specification for MLH1; this criterion is not available under the governing VCEP framework. Details ▾Hide ▴
Evidence considered
- PS5 is not a recognized criterion in the InSiGHT MLH1 VCEP v2.0 ruleset.
Sources
Identifiers
- Gene
- MLH1
- Transcript
- NM_000249.3
- Coding (HGVS c.)
- NM_000249.3:c.1738G>A
- Protein (HGVS p.)
- NP_000240.1:p.(Ala580Thr)
- GRCh38
- chr3:37047525 G>A
- GRCh37
- chr3:37089016 G>A
- ClinVar
- 3893982, 405428
- COSMIC
- COSV51614640
Gene diagram
Every interpreted variant in MLH1, mapped onto the exon structure of NM_000249.3. Select a row to find it on the plot.
MLH1NM_000249.3
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in MLH1
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
2 / 1,614,160 alleles
AF 1.24e-06 · 0 homozygotes · FAF 2.8e-07
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.2e-06 · 2 / 1,614,160 alleles · 0 hom · FAF 2.8e-07
| European (non-Finnish)2 / 1,179,992 | 1.7e-06 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.23903e-06; MAF= 0.00012%, 2/1614160 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.69493e-06; MAF= 0.00017%, 2/1179992 alleles, homozygotes = 0); grpmax FAF= 2.8e-07.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.703
- BayesDel
- 0.291
How the predictions were used
PP3 SupportingThe HCI prior probability for pathogenicity for p.Ala580Thr is 0.8146, which falls in the PP3_Supporting range (>0.68 and ≤0.81) per the InSiGHT VCEP v2.0 specification. SpliceAI predicts no splicing impact (max delta score 0.00), so the splice-based PP3 rule does not apply. REVEL score is 0.703 and BayesDel score is 0.291. Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.8146
- meeting VCEP PP3_Supporting threshold (>0.68
- ≤0.81).
- SpliceAI max delta = 0.00
- no predicted splice impact.
- REVEL = 0.703.
Sources
BP4 The HCI prior probability for pathogenicity for p.Ala580Thr is 0.8146, which is well above the VCEP BP4_Supporting threshold of <0.11. REVEL score is 0.703 and BayesDel score is 0.291, which do not suggest a benign in silico profile. SpliceAI predicts no splice impact (delta 0.00), but the BP4 splice rule applies only to intronic and synonymous variants, not missense. Details ▾Hide ▴
Evidence considered
- HCI prior = 0.8146
- far above BP4 threshold of <0.11.
- REVEL = 0.703
- in the intermediate range.
- SpliceAI delta = 0.00
- but BP4 splice rule is for intronic/synonymous variants only.
Sources
BP7 N/ABP7 applies only to synonymous (silent) or intronic variants at or beyond positions -21/+7. NM_000249.3:c.1738G>A is a missense variant (p.Ala580Thr) in exon 16 and does not qualify for BP7. Details ▾Hide ▴
Evidence considered
- Missense substitution
- BP7 is restricted to synonymous and intronic variants.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.703. BayesDel score = 0.291065. HCI prior probability for pathogenicity = 0.8146. MAPP score = 33.24. Custom PP2 score = 0.64.
7 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
-
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.Standards and guidelines for the interpretation of sequence variants (ACMG/AMP 2015). Provides the generic framework for variant classification. NM_000249.3:c.1738G>A was not identified in this paper.Does not name this variant
-
PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004Genetic cancer risk assessment and counseling recommendations from the National Society of Genetic Counselors. Discusses counseling frameworks without variant-specific data. NM_000249.3:c.1738G>A was not identified in the abstract.Does not name this variant
-
PMID 20301390 ↗Lynch Syndrome.Adam MP et al. · 1993Lynch Syndrome GeneReviews entry. General clinical synopsis of Lynch syndrome. No abstract or full text containing variant-specific data was available. NM_000249.3:c.1738G>A was not identified.Does not name this variant
-
PMID 23788249 ↗ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.ACMG recommendations for reporting incidental findings in clinical exome and genome sequencing. Discusses policy for secondary findings but does not evaluate or mention specific MLH1 variants. NM_000249.3:c.1738G>A was not identified.Does not name this variant
-
PMID 24310308 ↗ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis).ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, FAP, MAP). Gene-level discussion of MLH1 and MMR genes. NM_000249.3:c.1738G>A was not identified in this paper.Does not name this variant
-
PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015Practice guideline for referral indications for cancer predisposition assessment from ACMG/NSGC. Provides referral criteria for cancer genetic consultation. NM_000249.3:c.1738G>A was not identified.Does not name this variant
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Background review of classification methodology. No full text available; not expected to contain variant-specific data.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
2 / 1,614,160 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
4 Uncertain significance · 1 Uncertain Significance · 1 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 ↗
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/405428/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/3-37089016-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr3-37047525-G-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/3-37047525-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000249.3%3Ac.1738…
- OncoKB ↗www.oncokb.org/gene/MLH1/A580T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=124265464
- 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= 1.23903e-06; MAF= 0.00012%, 2/1614160 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.69493e-06; MAF= 0.00017%, 2/1179992 alleles, homozygotes = 0); grpmax FAF= 2.8e-07.
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 Uncertain significance (4 clinical laboratories) and as Uncertain Significance (1 clinical laboratory) and as Likely benign (1 clinical laboratory). (ClinVarID = 405428)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.703. BayesDel score = 0.291065. HCI prior probability for pathogenicity = 0.8146. MAPP score = 33.24. Custom PP2 score = 0.64.
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 previously been reported in somatic cancers (COSMIC; COSV51614640, n = 2 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.