NM_000179.3(MSH6):c.680G>T (p.Ser227Ile) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 2, 2019
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:: RCV000075024.11

Allele description [Variation Report for NM_000179.3(MSH6):c.680G>T (p.Ser227Ile)]

NM_000179.3(MSH6):c.680G>T (p.Ser227Ile)

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.680G>T (p.Ser227Ile)

HGVS:

NC_000002.12:g.47798663G>T
NG_007111.1:g.20517G>T
NM_000179.3:c.680G>TMANE SELECT
NM_001281492.2:c.290G>T
NM_001281493.2:c.-227G>T
NM_001281494.2:c.-227G>T
NP_000170.1:p.Ser227Ile
NP_000170.1:p.Ser227Ile
NP_001268421.1:p.Ser97Ile
LRG_219t1:c.680G>T
LRG_219:g.20517G>T
LRG_219p1:p.Ser227Ile
NC_000002.11:g.48025802G>T
NM_000179.2:c.680G>T

Protein change:

S227I

Links:

dbSNP: rs587779317

NCBI 1000 Genomes Browser:

rs587779317

Molecular consequence:

NM_001281493.2:c.-227G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281494.2:c.-227G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.680G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.290G>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
SCV000259596	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 2, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21437237, 16341805, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000259596

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 2, 2019)

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

Cooperative nuclear localization sequences lend a novel role to the N-terminal region of MSH6.

Gassman NR, Clodfelter JE, McCauley AK, Bonin K, Salsbury FR Jr, Scarpinato KD.

PLoS One. 2011 Mar 17;6(3):e17907. doi: 10.1371/journal.pone.0017907.

PubMed [citation]

PMID:: 21437237
PMCID:: PMC3060103

Mutational analysis of hMsh6 in Israeli HNPCC and HNPCC-like families.

Dovrat S, Figer A, Fidder HH, Neophytou P, Fireman Z, Geva R, Zidan J, Flex D, Meir SB, Friedman E.

Fam Cancer. 2005;4(4):291-4.

PubMed [citation]

PMID:: 16341805

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000259596.7

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

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. This variant has been reported not to substantially affect MSH6 protein function (PMID: 21437237). This variant has been observed in a family affected with colorectal cancer (PMID: 16341805). ClinVar contains an entry for this variant (Variation ID: 89555). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with isoleucine at codon 227 of the MSH6 protein (p.Ser227Ile). The serine residue is weakly conserved and there is a large physicochemical difference between serine and isoleucine.

#	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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