NM_000249.4(MLH1):c.637G>A (p.Val213Met) AND Hereditary cancer-predisposing syndrome

Germline classification:: Benign (5 submissions)
Last evaluated:: Nov 15, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000128927.13

Allele description [Variation Report for NM_000249.4(MLH1):c.637G>A (p.Val213Met)]

NM_000249.4(MLH1):c.637G>A (p.Val213Met)

Gene:

MLH1:mutL homolog 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.637G>A (p.Val213Met)

Other names:

p.V213M:GTG>ATG

HGVS:

NC_000003.12:g.37012059G>A
NG_007109.2:g.23710G>A
NM_000249.4:c.637G>AMANE SELECT
NM_001167617.3:c.343G>A
NM_001167618.3:c.-87G>A
NM_001167619.3:c.-87G>A
NM_001258271.2:c.637G>A
NM_001258273.2:c.-87G>A
NM_001258274.3:c.-87G>A
NM_001354615.2:c.-87G>A
NM_001354616.2:c.-87G>A
NM_001354617.2:c.-87G>A
NM_001354618.2:c.-87G>A
NM_001354619.2:c.-87G>A
NM_001354620.2:c.343G>A
NM_001354621.2:c.-180G>A
NM_001354622.2:c.-293G>A
NM_001354623.2:c.-293G>A
NM_001354624.2:c.-190G>A
NM_001354625.2:c.-190G>A
NM_001354626.2:c.-190G>A
NM_001354627.2:c.-190G>A
NM_001354628.2:c.637G>A
NM_001354629.2:c.538G>A
NM_001354630.2:c.637G>A
NP_000240.1:p.Val213Met
NP_000240.1:p.Val213Met
NP_001161089.1:p.Val115Met
NP_001245200.1:p.Val213Met
NP_001341549.1:p.Val115Met
NP_001341557.1:p.Val213Met
NP_001341558.1:p.Val180Met
NP_001341559.1:p.Val213Met
LRG_216t1:c.637G>A
LRG_216:g.23710G>A
LRG_216p1:p.Val213Met
NC_000003.11:g.37053550G>A
NM_000249.3:c.637G>A
NM_001167617.1:c.343G>A
P40692:p.Val213Met
p.V213M

Protein change:

V115M

Links:

UniProtKB: P40692#VAR_012910; dbSNP: rs2308317

NCBI 1000 Genomes Browser:

rs2308317

Molecular consequence:

NM_001167618.3:c.-87G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-87G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-87G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-87G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-87G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-87G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-87G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-87G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-87G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-180G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-293G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-293G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-190G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-190G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-190G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-190G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.637G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.343G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.637G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.343G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.637G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.538G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.637G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000172797	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Benign (Oct 22, 2014)	germline	clinical testing	Citation Link,
SCV000684855	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jan 1, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000788025	True Health Diagnostics	no assertion criteria provided	Benign (Nov 14, 2017)	germline	clinical testing
SCV002528764	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Benign (Oct 9, 2020)	germline	curation	Citation Link,
SCV002819213	Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Nov 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

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.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000172797.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV000684855.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From True Health Diagnostics, SCV000788025.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Sema4, Sema4, SCV002528764.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C., SCV002819213.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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