NM_000249.3(MLH1):c.194G>T (p.Gly65Val) AND Lynch syndrome

Clinical significance:Uncertain significance (Last evaluated: Jul 13, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000469604.1

Allele description [Variation Report for NM_000249.3(MLH1):c.194G>T (p.Gly65Val)]

NM_000249.3(MLH1):c.194G>T (p.Gly65Val)

Gene:
MLH1:mutL homolog 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p22.2
Genomic location:
Preferred name:
NM_000249.3(MLH1):c.194G>T (p.Gly65Val)
HGVS:
  • NC_000003.12:g.36996696G>T
  • NG_007109.2:g.8347G>T
  • NM_000249.3:c.194G>T
  • NM_001167617.1:c.-96G>T
  • NM_001258273.1:c.-517+3033G>T
  • NP_000240.1:p.Gly65Val
  • LRG_216t1:c.194G>T
  • LRG_216:g.8347G>T
  • LRG_216p1:p.Gly65Val
  • NC_000003.11:g.37038187G>T
Protein change:
G65V
Links:
dbSNP: rs63751465
NCBI 1000 Genomes Browser:
rs63751465
Molecular consequence:
  • NM_001167617.1:c.-96G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258273.1:c.-517+3033G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000249.3:c.194G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Lynch syndrome (HNPCC)
Synonyms:
Hereditary nonpolyposis colon cancer
Identifiers:
MedGen: C1333990; OMIM: PS120435

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000543649Invitaecriteria provided, single submitter
Uncertain significance
(Jul 13, 2016)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000543649.2

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

Description

This sequence change replaces glycine with valine at codon 65 of the MLH1 protein (p.Gly65Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 218021). Experimental studies have shown that this missense change adversely impacts MLH1 protein function (PMID: 15475387). In summary, this variant is a novel missense change that has been reported to disrupt MLH1 protein function, however additional genetic evidence is needed to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 10, 2018