ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3079G>C (p.Val1027Leu) (rs876658397)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216842 SCV000273550 likely benign Hereditary cancer-predisposing syndrome 2018-05-24 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Invitae RCV001080207 SCV000283782 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-11-23 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000227272 SCV001134420 uncertain significance not provided 2018-08-13 criteria provided, single submitter clinical testing
Color Health, Inc RCV000216842 SCV001359122 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-16 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000503628 SCV000592621 uncertain significance Carcinoma of colon no assertion criteria provided clinical testing The MSH6 p.Val1027Leu variant was not identified in the literature, nor was it identified in the dbSNP, NHLBI Exome Sequencing Project, Exome Aggregation Consortium (March 14, 2016), COSMIC, ClinVar, Clinvitae, GeneInsight COGR, MutDB, Mismatch Repair Genes Variant, MMR Gene Unclassified Variants, UMD Colon Cancer, InSIGHT Colon Cancer or Zhejiang Databases. The variant was identified on the LOVD-MSH6 variant database classified as “Unknown”. The p.Val1027 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. The c.3079G>C variant occurs outside of the splicing consensus sequence and 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, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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