ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1869C>T (p.Pro623=) (rs141242295)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212654 SCV000211354 benign not specified 2014-08-04 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 RCV000160720 SCV000212767 likely benign Hereditary cancer-predisposing syndrome 2014-11-17 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.
Invitae RCV001083167 SCV000252625 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-06 criteria provided, single submitter clinical testing
Counsyl RCV000411521 SCV000488443 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-03-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212654 SCV000601520 likely benign not specified 2016-10-13 criteria provided, single submitter clinical testing
Color Health, Inc RCV000160720 SCV000685236 likely benign Hereditary cancer-predisposing syndrome 2015-06-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759846 SCV000889462 benign not provided 2017-09-26 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355353 SCV001550221 benign Malignant tumor of breast no assertion criteria provided clinical testing The MSH6 p.Pro623= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, Cosmic, MutDB, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, Insight Hereditary Tumors Database databases. The variant was identified in dbSNP (ID: rs141242295) “With Likely benign allele”, ClinVar (classified benign by GeneDx, Invitae and likely benign by Ambry Genetics, Counsyl and Quest Diagnostics Nichols Institute San Juan Capistrano), Clinvitae (4x), UMD-LSDB (2x as UV), and in control databases in 77 (1 homozygous) of 276602 chromosomes at a frequency of 0.0003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 53 (1 homozygous) of 23906 chromosomes (freq: 0.002), Other in 1 of 6460 chromosomes (freq: 0.00002), Latino in 9 of 34400 chromosomes (freq: 0.0003), East Asian in 7 of 18854 chromosomes (freq: 0.0004), and South Asian in 7 of 30774 chromosomes (freq: 0.0002) while not observed in the European Non-Finnish, Ashkenazi Jewish and European Finnish populations. The p.Pro623= 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, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

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