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NM_000179.3(MSH6):c.909G>A (p.Met303Ile) AND Lynch syndrome 5

Germline classification:
Uncertain significance (1 submission)
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:
RCV003338803.2

Allele description [Variation Report for NM_000179.3(MSH6):c.909G>A (p.Met303Ile)]

NM_000179.3(MSH6):c.909G>A (p.Met303Ile)

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.909G>A (p.Met303Ile)
HGVS:
  • NC_000002.12:g.47798892G>A
  • NG_007111.1:g.20746G>A
  • NM_000179.3:c.909G>AMANE SELECT
  • NM_001281492.2:c.519G>A
  • NM_001281493.2:c.3G>A
  • NM_001281494.2:c.3G>A
  • NP_000170.1:p.Met303Ile
  • NP_000170.1:p.Met303Ile
  • NP_001268421.1:p.Met173Ile
  • NP_001268422.1:p.Met1Ile
  • NP_001268423.1:p.Met1Ile
  • LRG_219t1:c.909G>A
  • LRG_219:g.20746G>A
  • LRG_219p1:p.Met303Ile
  • NC_000002.11:g.48026031G>A
  • NM_000179.2:c.909G>A
Protein change:
M173I
Links:
dbSNP: rs786201688
NCBI 1000 Genomes Browser:
rs786201688
Molecular consequence:
  • NM_001281493.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001281494.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_000179.3:c.909G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.2:c.519G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Lynch syndrome 5 (LYNCH5)
Synonyms:
Colorectal cancer, hereditary nonpolyposis, type 5; Hereditary non-polyposis colorectal cancer, type 5
Identifiers:
MONDO: MONDO:0013710; MedGen: C1833477; Orphanet: 144; OMIM: 614350

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004047009Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significancegermlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot 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 Neuberg Centre For Genomic Medicine, NCGM, SCV004047009.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The missense variant in c.909G>A (p.Met303Ile) in MSH6 (NM_000179.2) gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Met303Ile variant is reported with the allele frequency (0.0003979 %) in the gnomad and novel in 1000 genome database. This variant has been reported to ClinVar database as Variant of Uncertain Significance (VUS). The amino acid Met at position 303 is changed to a Ile changing protein sequence and it might alter its composition and physico-chemical properties. In silico tools predict the variant to be tolerated. The residue is variable across species. The amino acid change p.Met303Ile in MSH6 is predicted as conserved by PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024