NM_000249.4(MLH1):c.637G>T (p.Val213Leu) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 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:: RCV000627709.7

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

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

HGVS:

NC_000003.12:g.37012059G>T
NG_007109.2:g.23710G>T
NM_000249.4:c.637G>TMANE SELECT
NM_001167617.3:c.343G>T
NM_001167618.3:c.-87G>T
NM_001167619.3:c.-87G>T
NM_001258271.2:c.637G>T
NM_001258273.2:c.-87G>T
NM_001258274.3:c.-87G>T
NM_001354615.2:c.-87G>T
NM_001354616.2:c.-87G>T
NM_001354617.2:c.-87G>T
NM_001354618.2:c.-87G>T
NM_001354619.2:c.-87G>T
NM_001354620.2:c.343G>T
NM_001354621.2:c.-180G>T
NM_001354622.2:c.-293G>T
NM_001354623.2:c.-293G>T
NM_001354624.2:c.-190G>T
NM_001354625.2:c.-190G>T
NM_001354626.2:c.-190G>T
NM_001354627.2:c.-190G>T
NM_001354628.2:c.637G>T
NM_001354629.2:c.538G>T
NM_001354630.2:c.637G>T
NP_000240.1:p.Val213Leu
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>T
LRG_216:g.23710G>T
LRG_216p1:p.Val213Leu
NC_000003.11:g.37053550G>T
NM_000249.3:c.637G>T

Protein change:

V115L

Links:

dbSNP: rs2308317

NCBI 1000 Genomes Browser:

rs2308317

Molecular consequence:

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

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000543572	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16810763, 17074586, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000543572

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families.

Wang XL, Yuan Y, Zhang SZ, Cai SR, Huang YQ, Jiang Q, Zheng S.

World J Gastroenterol. 2006 Jul 7;12(25):4074-7.

PubMed [citation]

PMID:: 16810763
PMCID:: PMC4087725

Single-nucleotide polymorphisms of mismatch repair genes in healthy Chinese individuals and sporadic colorectal cancer patients.

Mei Q, Yan HL, Ding FX, Xue G, Huang JJ, Wang YZ, Sun SH.

Cancer Genet Cytogenet. 2006 Nov;171(1):17-23.

PubMed [citation]

PMID:: 17074586

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000543572.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

ClinVar contains an entry for this variant (Variation ID: 90300). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MLH1 protein function. This missense change has been observed in individual(s) with hereditary non-polyposis colorectal cancer (HNPCC) (PMID: 16810763, 17074586). This variant is present in population databases (rs2308317, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 213 of the MLH1 protein (p.Val213Leu).

#	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

ClinVar

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