NM_000179.3(MSH6):c.3610G>A (p.Ala1204Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 1, 2021
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:: RCV001020725.3

Allele description [Variation Report for NM_000179.3(MSH6):c.3610G>A (p.Ala1204Thr)]

NM_000179.3(MSH6):c.3610G>A (p.Ala1204Thr)

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.3610G>A (p.Ala1204Thr)

HGVS:

NC_000002.12:g.47805671G>A
NG_007111.1:g.27525G>A
NG_008397.1:g.105005C>T
NM_000179.3:c.3610G>AMANE SELECT
NM_001281492.2:c.3220G>A
NM_001281493.2:c.2704G>A
NM_001281494.2:c.2704G>A
NP_000170.1:p.Ala1204Thr
NP_000170.1:p.Ala1204Thr
NP_001268421.1:p.Ala1074Thr
NP_001268422.1:p.Ala902Thr
NP_001268423.1:p.Ala902Thr
LRG_219t1:c.3610G>A
LRG_219:g.27525G>A
LRG_219p1:p.Ala1204Thr
NC_000002.11:g.48032810G>A
NM_000179.2:c.3610G>A

Protein change:

A1074T

Links:

dbSNP: rs869312799

NCBI 1000 Genomes Browser:

rs869312799

Molecular consequence:

NM_000179.3:c.3610G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.3220G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.2704G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.2704G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

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Chain G, Protein Trav14-1,T-cell receptor alpha chain C region
Chain G, Protein Trav14-1,T-cell receptor alpha chain C region
gi|1321390702|pdb|5M02|G

Protein
FXN [Bos indicus]
FXN [Bos indicus]
Gene ID:109562939

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001182238	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001182238

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 1, 2021)

germline

clinical testing

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

Citation Link

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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

Improving performance of multigene panels for genomic analysis of cancer predisposition.

Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC.

Genet Med. 2016 Oct;18(10):974-81. doi: 10.1038/gim.2015.212. Epub 2016 Feb 4.

PubMed [citation]

PMID:: 26845104

Details of each submission

From Ambry Genetics, SCV001182238.4

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

Description

The p.A1204T variant (also known as c.3610G>A), located in coding exon 7 of the MSH6 gene, results from a G to A substitution at nucleotide position 3610. The alanine at codon 1204 is replaced by threonine, an amino acid with similar properties. This alteration was detected in an individual with fallopian tube cancer that had intact staining for the mismatch repair genes by immunohistochemistry (IHC) (Shirts BH et al. Genet Med, 2016 10;18:974-81). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 8, 2024

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