U.S. flag

An official website of the United States government

NM_000179.3(MSH6):c.3740C>G (p.Thr1247Ser) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 30, 2018
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:
RCV000780480.1

Allele description [Variation Report for NM_000179.3(MSH6):c.3740C>G (p.Thr1247Ser)]

NM_000179.3(MSH6):c.3740C>G (p.Thr1247Ser)

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.3740C>G (p.Thr1247Ser)
HGVS:
  • NC_000002.12:g.47806297C>G
  • NG_007111.1:g.28151C>G
  • NG_008397.1:g.104379G>C
  • NM_000179.3:c.3740C>GMANE SELECT
  • NM_001281492.2:c.3350C>G
  • NM_001281493.2:c.2834C>G
  • NM_001281494.2:c.2834C>G
  • NP_000170.1:p.Thr1247Ser
  • NP_000170.1:p.Thr1247Ser
  • NP_001268421.1:p.Thr1117Ser
  • NP_001268422.1:p.Thr945Ser
  • NP_001268423.1:p.Thr945Ser
  • LRG_219t1:c.3740C>G
  • LRG_219:g.28151C>G
  • LRG_219p1:p.Thr1247Ser
  • NC_000002.11:g.48033436C>G
  • NM_000179.2:c.3740C>G
Protein change:
T1117S
Links:
dbSNP: rs786204182
NCBI 1000 Genomes Browser:
rs786204182
Molecular consequence:
  • NM_000179.3:c.3740C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.2:c.3350C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.2:c.2834C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.2:c.2834C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000917764Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(May 30, 2018) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917764.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: MSH6 c.3740C>G (p.Thr1247Ser) results in a conservative amino acid change located in the DNA mismatch repair protein MutS, C-terminal of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245976 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3740C>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "uncertain significance." Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: May 7, 2024