U.S. flag

An official website of the United States government

NM_000179.3(MSH6):c.3524C>T (p.Thr1175Ile) AND Lynch syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 28, 2023
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:
RCV004003383.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3524C>T (p.Thr1175Ile)]

NM_000179.3(MSH6):c.3524C>T (p.Thr1175Ile)

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.3524C>T (p.Thr1175Ile)
HGVS:
  • NC_000002.12:g.47804995C>T
  • NG_007111.1:g.26849C>T
  • NG_008397.1:g.105681G>A
  • NM_000179.3:c.3524C>TMANE SELECT
  • NM_001281492.2:c.3134C>T
  • NM_001281493.2:c.2618C>T
  • NM_001281494.2:c.2618C>T
  • NP_000170.1:p.Thr1175Ile
  • NP_000170.1:p.Thr1175Ile
  • NP_001268421.1:p.Thr1045Ile
  • NP_001268422.1:p.Thr873Ile
  • NP_001268423.1:p.Thr873Ile
  • LRG_219t1:c.3524C>T
  • LRG_219:g.26849C>T
  • LRG_219p1:p.Thr1175Ile
  • NC_000002.11:g.48032134C>T
  • NM_000179.2:c.3524C>T
Protein change:
T1045I
Links:
dbSNP: rs369583604
NCBI 1000 Genomes Browser:
rs369583604
Molecular consequence:
  • NM_000179.3:c.3524C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.2:c.3134C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.2:c.2618C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.2:c.2618C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Lynch syndrome
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100

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
SCV004835084All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Jun 28, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not 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 All of Us Research Program, National Institutes of Health, SCV004835084.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

This missense variant replaces threonine with isoleucine at codon 1175 of the MSH6 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/282662 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024