NM_000251.3(MSH2):c.1831G>A (p.Val611Met) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2023
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:: RCV000232146.10

Allele description [Variation Report for NM_000251.3(MSH2):c.1831G>A (p.Val611Met)]

NM_000251.3(MSH2):c.1831G>A (p.Val611Met)

Gene:

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.1831G>A (p.Val611Met)

HGVS:

NC_000002.12:g.47475096G>A
NG_007110.2:g.76973G>A
NM_000251.3:c.1831G>AMANE SELECT
NM_001258281.1:c.1633G>A
NP_000242.1:p.Val611Met
NP_000242.1:p.Val611Met
NP_001245210.1:p.Val545Met
LRG_218t1:c.1831G>A
LRG_218:g.76973G>A
LRG_218p1:p.Val611Met
NC_000002.11:g.47702235G>A
NM_000251.1:c.1831G>A
NM_000251.2:c.1831G>A

Protein change:

V545M

Links:

dbSNP: rs369385048

NCBI 1000 Genomes Browser:

rs369385048

Molecular consequence:

NM_000251.3:c.1831G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.1633G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Homo sapiens copine I (CPNE1), transcript variant 5, mRNA
Homo sapiens copine I (CPNE1), transcript variant 5, mRNA
gi|23397701|ref|NM_152928.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000284124	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31159747, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000284124

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2023)

germline

clinical testing

PubMed (2)
[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

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

Tsaousis GN, Papadopoulou E, Apessos A, Agiannitopoulos K, Pepe G, Kampouri S, Diamantopoulos N, Floros T, Iosifidou R, Katopodi O, Koumarianou A, Markopoulos C, Papazisis K, Venizelos V, Xanthakis I, Xepapadakis G, Banu E, Eniu DT, Negru S, Stanculeanu DL, Ungureanu A, Ozmen V, et al.

BMC Cancer. 2019 Jun 3;19(1):535. doi: 10.1186/s12885-019-5756-4.

PubMed [citation]

PMID:: 31159747
PMCID:: PMC6547505

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000284124.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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 MSH2 protein function. ClinVar contains an entry for this variant (Variation ID: 237376). This missense change has been observed in individual(s) with personal or family history of cancer (PMID: 31159747). This variant is present in population databases (rs369385048, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 611 of the MSH2 protein (p.Val611Met).

#	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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