NM_000179.3(MSH6):c.2225A>G (p.Asn742Ser) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 5, 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:: RCV002230106.12

Allele description [Variation Report for NM_000179.3(MSH6):c.2225A>G (p.Asn742Ser)]

NM_000179.3(MSH6):c.2225A>G (p.Asn742Ser)

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.2225A>G (p.Asn742Ser)

HGVS:

NC_000002.12:g.47800208A>G
NG_007111.1:g.22062A>G
NM_000179.3:c.2225A>GMANE SELECT
NM_001281492.2:c.1835A>G
NM_001281493.2:c.1319A>G
NM_001281494.2:c.1319A>G
NP_000170.1:p.Asn742Ser
NP_000170.1:p.Asn742Ser
NP_001268421.1:p.Asn612Ser
NP_001268422.1:p.Asn440Ser
NP_001268423.1:p.Asn440Ser
LRG_219t1:c.2225A>G
LRG_219:g.22062A>G
LRG_219p1:p.Asn742Ser
NC_000002.11:g.48027347A>G
NM_000179.2:c.2225A>G

Protein change:

N440S

Links:

dbSNP: rs878853715

NCBI 1000 Genomes Browser:

rs878853715

Molecular consequence:

NM_000179.3:c.2225A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.1835A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.1319A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.1319A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Mus musculus CD300 antigen like family member G, mRNA (cDNA clone MGC:151283 IMA...
Mus musculus CD300 antigen like family member G, mRNA (cDNA clone MGC:151283 IMAGE:40126225), complete cds
gi|109734167|gb|BC116906.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000551092	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 5, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26976419, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000551092

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 5, 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

Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.

Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE.

J Clin Oncol. 2016 May 1;34(13):1460-8. doi: 10.1200/JCO.2015.65.0747. Epub 2016 Mar 14.

PubMed [citation]

PMID:: 26976419
PMCID:: PMC4872307

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, SCV000551092.5

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

Description

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 742 of the MSH6 protein (p.Asn742Ser). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MSH6 protein function. ClinVar contains an entry for this variant (Variation ID: 410422). This missense change has been observed in individual(s) with breast cancer (PMID: 26976419). This variant is not present in population databases (gnomAD no frequency).

#	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 26, 2024

ClinVar

Relating variation to medicine