NM_000179.3(MSH6):c.3478G>C (p.Val1160Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 18, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000129922.7

Allele description [Variation Report for NM_000179.3(MSH6):c.3478G>C (p.Val1160Leu)]

NM_000179.3(MSH6):c.3478G>C (p.Val1160Leu)

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.3478G>C (p.Val1160Leu)

HGVS:

NC_000002.12:g.47804949G>C
NG_007111.1:g.26803G>C
NG_008397.1:g.105727C>G
NM_000179.3:c.3478G>CMANE SELECT
NM_001281492.2:c.3088G>C
NM_001281493.2:c.2572G>C
NM_001281494.2:c.2572G>C
NP_000170.1:p.Val1160Leu
NP_000170.1:p.Val1160Leu
NP_001268421.1:p.Val1030Leu
NP_001268422.1:p.Val858Leu
NP_001268423.1:p.Val858Leu
LRG_219t1:c.3478G>C
LRG_219:g.26803G>C
LRG_219p1:p.Val1160Leu
NC_000002.11:g.48032088G>C
NM_000179.2:c.3478G>C
p.V1160L

Protein change:

V1030L

Links:

dbSNP: rs376799914

NCBI 1000 Genomes Browser:

rs376799914

Molecular consequence:

NM_000179.3:c.3478G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.3088G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.2572G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.2572G>C - 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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F-box SKIP23-like protein (DUF295) [Arabidopsis thaliana]
F-box SKIP23-like protein (DUF295) [Arabidopsis thaliana]
gi|1063713730|ref|NP_001325458.1|

Protein
Cryptodira RNA fingerprint protein 35 (R35) gene, intron 1.
Cryptodira RNA fingerprint protein 35 (R35) gene, intron 1.
PopSet: 403309778

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000184740	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 14, 2021)	germline	clinical testing	Citation Link,
SCV002528035	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Mar 18, 2022)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 32980694, 33471991 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000184740

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 14, 2021)

germline

clinical testing

Citation Link,

SCV002528035

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Mar 18, 2022)

germline

curation

PubMed (2)
[See all records that cite these PMIDs]

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, curation

Citations

PubMed

Genetic characterization of pancreatic cancer patients and prediction of carrier status of germline pathogenic variants in cancer-predisposing genes.

Mizukami K, Iwasaki Y, Kawakami E, Hirata M, Kamatani Y, Matsuda K, Endo M, Sugano K, Yoshida T, Murakami Y, Nakagawa H, Spurdle AB, Momozawa Y.

EBioMedicine. 2020 Oct;60:103033. doi: 10.1016/j.ebiom.2020.103033. Epub 2020 Sep 24.

PubMed [citation]

PMID:: 32980694
PMCID:: PMC7519363

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

Details of each submission

From Ambry Genetics, SCV000184740.8

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

Description

The p.V1160L variant (also known as c.3478G>C), located in coding exon 6 of the MSH6 gene, results from a G to C substitution at nucleotide position 3478. The valine at codon 1160 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well 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

From Sema4, Sema4, SCV002528035.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

#	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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