NM_000179.3(MSH6):c.899G>T (p.Arg300Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 12, 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:: RCV000166713.5

Allele description [Variation Report for NM_000179.3(MSH6):c.899G>T (p.Arg300Leu)]

NM_000179.3(MSH6):c.899G>T (p.Arg300Leu)

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.899G>T (p.Arg300Leu)

HGVS:

NC_000002.12:g.47798882G>T
NG_007111.1:g.20736G>T
NM_000179.3:c.899G>TMANE SELECT
NM_001281492.2:c.509G>T
NM_001281493.2:c.-8G>T
NM_001281494.2:c.-8G>T
NP_000170.1:p.Arg300Leu
NP_000170.1:p.Arg300Leu
NP_001268421.1:p.Arg170Leu
LRG_219t1:c.899G>T
LRG_219:g.20736G>T
LRG_219p1:p.Arg300Leu
NC_000002.11:g.48026021G>T
NM_000179.2:c.899G>T
p.R300L

Protein change:

R170L

Links:

dbSNP: rs55760494

NCBI 1000 Genomes Browser:

rs55760494

Molecular consequence:

NM_001281493.2:c.-8G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281494.2:c.-8G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.899G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.509G>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000217523	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 12, 2022)	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

SCV000217523

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 12, 2022)

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

Outcomes of retesting BRCA negative patients using multigene panels.

Yadav S, Reeves A, Campian S, Paine A, Zakalik D.

Fam Cancer. 2017 Jul;16(3):319-328. doi: 10.1007/s10689-016-9956-7.

PubMed [citation]

PMID:: 27878467

Details of each submission

From Ambry Genetics, SCV000217523.7

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

Description

The p.R300L variant (also known as c.899G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 899. The arginine at codon 300 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been detected in a cohort of 122 patients who underwent multi-gene panel testing for hereditary cancer after having previously tested negative for mutations in BRCA1 and BRCA2 (Yadav S et al. Fam. Cancer, 2017 07;16:319-328). 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: Sep 29, 2024

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