Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000160666 | SCV000211276 | uncertain significance | not provided | 2023-08-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27460824, 27882345, 17531815, 21120944) |
Invitae | RCV000195871 | SCV000254271 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000563544 | SCV000669921 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-15 | criteria provided, single submitter | clinical testing | The p.S405C variant (also known as c.1214C>G), located in coding exon 4 of the MSH6 gene, results from a C to G substitution at nucleotide position 1214. The serine at codon 405 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780479 | SCV000917763 | uncertain significance | not specified | 2018-05-25 | criteria provided, single submitter | clinical testing | Variant summary: MSH6 c.1214C>G (p.Ser405Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246082 control chromosomes. This frequency is not higher than expected for a pathogenic variant in MSH6 causing Lynch Syndrome (8.1e-06 vs 0.00014), allowing no conclusion about variant significance. c.1214C>G has been reported in the literature (Garofalo 2016), however, this report does not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Color Diagnostics, |
RCV000563544 | SCV001344149 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-07 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003998492 | SCV004835364 | uncertain significance | Lynch syndrome | 2023-11-28 | criteria provided, single submitter | clinical testing |