ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3265T>C (p.Leu1089=) (rs34490141)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164765 SCV000215441 benign Hereditary cancer-predisposing syndrome 2014-07-11 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Invitae RCV001081375 SCV000259406 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-04 criteria provided, single submitter clinical testing
Color Health, Inc RCV000164765 SCV000685381 likely benign Hereditary cancer-predisposing syndrome 2015-04-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589050 SCV000695848 benign not provided 2016-01-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589050 SCV000888270 benign not provided 2018-03-05 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356967 SCV001552274 likely benign Carcinoma of colon no assertion criteria provided clinical testing The MSH6 p.Leu1089= variant was not identified in the literature nor was it identified in the UMD-LSDB database. The variant was identified in dbSNP (rs34490141) as “with other allele and ClinVar (classified as benign by Invitae, Ambry Genetics, Integrated Genetics and 1 other submitter; and as likely benign by Color). The variant was identified in control databases in 90 of 282,832 chromosomes at a frequency of 0.0003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 84 of 24,974 chromosomes (freq: 0.003, increasing the likelihood this could be a low frequency benign variant), Latino in 4 of 35,422 chromosomes (freq: 0.0001), South Asian in 1 of 30,616 chromosomes (freq: 0.00003), and European in 1 of 129,162 chromosomes (freq: 0.000008), while it was not observed in the Ashkenazi Jewish, East Asian, Finnish or Other populations. The p.Leu1089= 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. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing; this is not very predictive of pathogenicity. 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.

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