NM_000179.3(MSH6):c.991T>A (p.Ser331Thr) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 15, 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:: RCV003094898.3

Allele description [Variation Report for NM_000179.3(MSH6):c.991T>A (p.Ser331Thr)]

NM_000179.3(MSH6):c.991T>A (p.Ser331Thr)

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.991T>A (p.Ser331Thr)

HGVS:

NC_000002.12:g.47798974T>A
NG_007111.1:g.20828T>A
NM_000179.3:c.991T>AMANE SELECT
NM_001281492.2:c.601T>A
NM_001281493.2:c.85T>A
NM_001281494.2:c.85T>A
NM_001406795.1:c.1087T>A
NM_001406796.1:c.991T>A
NM_001406797.1:c.694T>A
NM_001406798.1:c.991T>A
NM_001406799.1:c.466T>A
NM_001406800.1:c.991T>A
NM_001406801.1:c.694T>A
NM_001406802.1:c.1087T>A
NM_001406803.1:c.991T>A
NM_001406804.1:c.913T>A
NM_001406805.1:c.694T>A
NM_001406806.1:c.466T>A
NM_001406807.1:c.466T>A
NM_001406808.1:c.991T>A
NM_001406809.1:c.991T>A
NM_001406811.1:c.85T>A
NM_001406812.1:c.85T>A
NM_001406813.1:c.997T>A
NM_001406814.1:c.85T>A
NM_001406815.1:c.85T>A
NM_001406816.1:c.85T>A
NM_001406817.1:c.991T>A
NM_001406818.1:c.694T>A
NM_001406819.1:c.694T>A
NM_001406820.1:c.694T>A
NM_001406821.1:c.694T>A
NM_001406822.1:c.694T>A
NM_001406823.1:c.85T>A
NM_001406824.1:c.694T>A
NM_001406825.1:c.694T>A
NM_001406826.1:c.823T>A
NM_001406827.1:c.694T>A
NM_001406828.1:c.694T>A
NM_001406829.1:c.85T>A
NM_001406830.1:c.694T>A
NP_000170.1:p.Ser331Thr
NP_000170.1:p.Ser331Thr
NP_001268421.1:p.Ser201Thr
NP_001268422.1:p.Ser29Thr
NP_001268423.1:p.Ser29Thr
NP_001393724.1:p.Ser363Thr
NP_001393725.1:p.Ser331Thr
NP_001393726.1:p.Ser232Thr
NP_001393727.1:p.Ser331Thr
NP_001393728.1:p.Ser156Thr
NP_001393729.1:p.Ser331Thr
NP_001393730.1:p.Ser232Thr
NP_001393731.1:p.Ser363Thr
NP_001393732.1:p.Ser331Thr
NP_001393733.1:p.Ser305Thr
NP_001393734.1:p.Ser232Thr
NP_001393735.1:p.Ser156Thr
NP_001393736.1:p.Ser156Thr
NP_001393737.1:p.Ser331Thr
NP_001393738.1:p.Ser331Thr
NP_001393740.1:p.Ser29Thr
NP_001393741.1:p.Ser29Thr
NP_001393742.1:p.Ser333Thr
NP_001393743.1:p.Ser29Thr
NP_001393744.1:p.Ser29Thr
NP_001393745.1:p.Ser29Thr
NP_001393746.1:p.Ser331Thr
NP_001393747.1:p.Ser232Thr
NP_001393748.1:p.Ser232Thr
NP_001393749.1:p.Ser232Thr
NP_001393750.1:p.Ser232Thr
NP_001393751.1:p.Ser232Thr
NP_001393752.1:p.Ser29Thr
NP_001393753.1:p.Ser232Thr
NP_001393754.1:p.Ser232Thr
NP_001393755.1:p.Ser275Thr
NP_001393756.1:p.Ser232Thr
NP_001393757.1:p.Ser232Thr
NP_001393758.1:p.Ser29Thr
NP_001393759.1:p.Ser232Thr
LRG_219t1:c.991T>A
LRG_219:g.20828T>A
LRG_219p1:p.Ser331Thr
NC_000002.11:g.48026113T>A
NM_000179.2:c.991T>A
NR_176257.1:n.1080T>A
NR_176258.1:n.1080T>A
NR_176259.1:n.1080T>A
NR_176261.1:n.1080T>A

Protein change:

S156T

Molecular consequence:

NM_000179.3:c.991T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.601T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.85T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.85T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406795.1:c.1087T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406796.1:c.991T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406797.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406798.1:c.991T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406799.1:c.466T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406800.1:c.991T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406801.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406802.1:c.1087T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406803.1:c.991T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406804.1:c.913T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406805.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406806.1:c.466T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406807.1:c.466T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406808.1:c.991T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406809.1:c.991T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406811.1:c.85T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406812.1:c.85T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406813.1:c.997T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406814.1:c.85T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406815.1:c.85T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406816.1:c.85T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406817.1:c.991T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406818.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406819.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406820.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406821.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406822.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406823.1:c.85T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406824.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406825.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406826.1:c.823T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406827.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406828.1:c.694T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406829.1:c.85T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406830.1:c.694T>A - 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

hs3st3l [Micropterus salmoides]
hs3st3l [Micropterus salmoides]
Gene ID:119916166

Gene

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
SCV003218873	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003218873

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2022)

germline

clinical testing

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

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

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, SCV003218873.2

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

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 MSH6 protein function. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 331 of the MSH6 protein (p.Ser331Thr).

#	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

Relating variation to medicine