NM_000179.3(MSH6):c.1368G>A (p.Trp456Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 9, 2018
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:: RCV001011198.3

Allele description [Variation Report for NM_000179.3(MSH6):c.1368G>A (p.Trp456Ter)]

NM_000179.3(MSH6):c.1368G>A (p.Trp456Ter)

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.1368G>A (p.Trp456Ter)

HGVS:

NC_000002.12:g.47799351G>A
NG_007111.1:g.21205G>A
NM_000179.3:c.1368G>AMANE SELECT
NM_001281492.2:c.978G>A
NM_001281493.2:c.462G>A
NM_001281494.2:c.462G>A
NP_000170.1:p.Trp456Ter
NP_001268421.1:p.Trp326Ter
NP_001268422.1:p.Trp154Ter
NP_001268423.1:p.Trp154Ter
LRG_219t1:c.1368G>A
LRG_219:g.21205G>A
NC_000002.11:g.48026490G>A
NM_000179.2:c.1368G>A

Protein change:

W154*

Links:

dbSNP: rs1572722737

NCBI 1000 Genomes Browser:

rs1572722737

Molecular consequence:

NM_000179.3:c.1368G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001281492.2:c.978G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001281493.2:c.462G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001281494.2:c.462G>A - nonsense - [Sequence Ontology: SO:0001587]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001171493	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 9, 2018)	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

SCV001171493

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 9, 2018)

germline

clinical testing

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

Citation Link

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

Prevalence of Lynch syndrome among patients with newly diagnosed endometrial cancers.

Egoavil C, Alenda C, Castillejo A, Paya A, Peiro G, Sánchez-Heras AB, Castillejo MI, Rojas E, Barberá VM, Cigüenza S, Lopez JA, Piñero O, Román MJ, Martínez-Escoriza JC, Guarinos C, Perez-Carbonell L, Aranda FI, Soto JL.

PLoS One. 2013;8(11):e79737. doi: 10.1371/journal.pone.0079737.

PubMed [citation]

PMID:: 24244552
PMCID:: PMC3820559

Details of each submission

From Ambry Genetics, SCV001171493.4

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

Description

The p.W456* pathogenic mutation (also known as c.1368G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 1368. This changes the amino acid from a tryptophan to a stop codon within coding exon 4. A similar mutation which causes the same protein truncation, c.1367G>A (p.W456*), has been reported in two unrelated endometrial cancer patients, including one who had a synchronous ovarian cancer diagnosis (Egoavil C et al. PLoS ONE, 2013 Nov;8:e79737). In addition to the clinical data presented in the literature, p.W456* (c.1368G>A) is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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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