NM_000249.4(MLH1):c.637G>C (p.Val213Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 2, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001025202.3

Allele description [Variation Report for NM_000249.4(MLH1):c.637G>C (p.Val213Leu)]

NM_000249.4(MLH1):c.637G>C (p.Val213Leu)

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>C (p.Val213Leu)

HGVS:

NC_000003.12:g.37012059G>C
NG_007109.2:g.23710G>C
NM_000249.4:c.637G>CMANE SELECT
NM_001167617.3:c.343G>C
NM_001167618.3:c.-87G>C
NM_001167619.3:c.-87G>C
NM_001258271.2:c.637G>C
NM_001258273.2:c.-87G>C
NM_001258274.3:c.-87G>C
NM_001354615.2:c.-87G>C
NM_001354616.2:c.-87G>C
NM_001354617.2:c.-87G>C
NM_001354618.2:c.-87G>C
NM_001354619.2:c.-87G>C
NM_001354620.2:c.343G>C
NM_001354621.2:c.-180G>C
NM_001354622.2:c.-293G>C
NM_001354623.2:c.-293G>C
NM_001354624.2:c.-190G>C
NM_001354625.2:c.-190G>C
NM_001354626.2:c.-190G>C
NM_001354627.2:c.-190G>C
NM_001354628.2:c.637G>C
NM_001354629.2:c.538G>C
NM_001354630.2:c.637G>C
NP_000240.1:p.Val213Leu
NP_001161089.1:p.Val115Leu
NP_001245200.1:p.Val213Leu
NP_001341549.1:p.Val115Leu
NP_001341557.1:p.Val213Leu
NP_001341558.1:p.Val180Leu
NP_001341559.1:p.Val213Leu
LRG_216t1:c.637G>C
LRG_216:g.23710G>C
NC_000003.11:g.37053550G>C
NC_000003.11:g.37053550G>C
NM_000249.3:c.637G>C

Protein change:

V115L

Links:

dbSNP: rs2308317

NCBI 1000 Genomes Browser:

rs2308317

Molecular consequence:

NM_001167618.3:c.-87G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-87G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-87G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-87G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-87G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-87G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-87G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-87G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-87G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-180G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-293G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-293G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-190G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-190G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-190G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-190G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.637G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.343G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.637G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.343G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.637G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.538G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.637G>C - 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
SCV001187343	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001187343

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 2, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

Citations

PubMed

Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods.

Arora S, Huwe PJ, Sikder R, Shah M, Browne AJ, Lesh R, Nicolas E, Deshpande S, Hall MJ, Dunbrack RL Jr, Golemis EA.

Cancer Biol Ther. 2017 Jul 3;18(7):519-533. doi: 10.1080/15384047.2017.1326439. Epub 2017 May 11.

PubMed [citation]

PMID:: 28494185
PMCID:: PMC5639829

Details of each submission

From Ambry Genetics, SCV001187343.4

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

Description

The p.V213L variant (also known as c.637G>C), located in coding exon 8 of the MLH1 gene, results from a G to C substitution at nucleotide position 637. The valine at codon 213 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Sep 29, 2024

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