NM_000179.2(MSH6):c.3079G>C (p.Val1027Leu) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Dec 16, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000216842.3

Allele description [Variation Report for NM_000179.2(MSH6):c.3079G>C (p.Val1027Leu)]

NM_000179.2(MSH6):c.3079G>C (p.Val1027Leu)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.2(MSH6):c.3079G>C (p.Val1027Leu)
HGVS:
  • NC_000002.12:g.47801062G>C
  • NG_007111.1:g.22916G>C
  • NM_000179.2:c.3079G>C
  • NM_001281492.1:c.2689G>C
  • NM_001281493.1:c.2173G>C
  • NM_001281494.1:c.2173G>C
  • NP_000170.1:p.Val1027Leu
  • NP_001268421.1:p.Val897Leu
  • NP_001268422.1:p.Val725Leu
  • NP_001268423.1:p.Val725Leu
  • LRG_219t1:c.3079G>C
  • LRG_219:g.22916G>C
  • LRG_219p1:p.Val1027Leu
  • NC_000002.11:g.48028201G>C
Protein change:
V1027L
Links:
dbSNP: rs876658397
NCBI 1000 Genomes Browser:
rs876658397
Molecular consequence:
  • NM_000179.2:c.3079G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.1:c.2689G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.1:c.2173G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.1:c.2173G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000273550Ambry Geneticscriteria provided, single submitter
Likely benign
(May 24, 2018)
germlineclinical testing

Citation Link,

SCV001359122Color Health, Inccriteria provided, single submitter
Uncertain significance
(Dec 16, 2019)
germlineclinical testing

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

Description

This missense variant replaces valine with leucine at codon 1027 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

SCV001359122

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV000273550.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

In silico models in agreement (benign);Other data supporting benign classification

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV001359122.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 6, 2021

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