ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1449G>T (p.Val483=) (rs35590297)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001084470 SCV000166209 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-01 criteria provided, single submitter clinical testing
GeneDx RCV000202140 SCV000170353 benign not specified 2014-02-25 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000126826 SCV000213008 likely benign Hereditary cancer-predisposing syndrome 2014-08-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Health, Inc RCV000126826 SCV000685194 likely benign Hereditary cancer-predisposing syndrome 2015-06-15 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000600196 SCV000744291 likely benign Hereditary nonpolyposis colorectal cancer type 5 2017-06-28 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000600196 SCV000745649 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-09-05 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679214 SCV000805843 likely benign not provided 2017-11-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679214 SCV000888239 benign not provided 2019-04-02 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000679214 SCV001152290 likely benign not provided 2019-01-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000600196 SCV001299858 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Mayo Clinic Laboratories, Mayo Clinic RCV000202140 SCV000257211 likely benign not specified no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000600196 SCV000734213 likely benign Hereditary nonpolyposis colorectal cancer type 5 no assertion criteria provided clinical testing
True Health Diagnostics RCV000126826 SCV000886688 likely benign Hereditary cancer-predisposing syndrome 2018-08-03 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356260 SCV001551377 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The MSH6 p.Val483= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs35590297) as "With other allele", ClinVar (classified as benign by Invitae and GeneDx; as likely benign by seven submitters), and in UMD-LSDB (2x as unclassified variant). The variant was identified in control databases in 92 of 276872 chromosomes at a frequency of 0.0003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 3 of 24024 chromosomes (freq: 0.0001), Other in 3 of 6462 chromosomes (freq: 0.0005), Latino in 4 of 34382 chromosomes (freq: 0.0001), European in 75 of 126426 chromosomes (freq: 0.0006), Finnish in 7 of 25794 chromosomes (freq: 0.0003); it was not observed in the Ashkenazi Jewish, East Asian, or South Asian populations. The p.Val483= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Clinical Genetics,Academic Medical Center RCV000679214 SCV001922359 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000679214 SCV001951063 likely benign not provided no assertion criteria provided clinical testing

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