Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000131253 | SCV000186215 | benign | Hereditary cancer-predisposing syndrome | 2023-10-26 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. |
Gene |
RCV000168415 | SCV000211269 | likely benign | not provided | 2020-02-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001086248 | SCV000219109 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131253 | SCV000902914 | benign | Hereditary cancer-predisposing syndrome | 2017-01-17 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000168415 | SCV001134385 | likely benign | not provided | 2020-11-12 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000212642 | SCV001519616 | benign | not specified | 2021-03-13 | criteria provided, single submitter | clinical testing | Variant summary: MSH6 c.1049C>T (p.Ala350Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00024 in 251258 control chromosomes. The observed variant frequency is approximately 1.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in MSH6 causing Lynch Syndrome phenotype (0.00014), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1049C>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A recent report evaluating a tumor characteristic likelihood ratio (TCLR) in combination with a multifactorial variant prediction (MVP) model predicted this variant to have a benign outcome (Li_2020). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign, n=2; likely benign, n=2; VUS, n=1). Based on the evidence outlined above, the variant was classified as benign. |
Genome Diagnostics Laboratory, |
RCV000212642 | SCV001977850 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000168415 | SCV001979311 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Prevention |
RCV004544297 | SCV004774860 | likely benign | MSH6-related disorder | 2023-05-19 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |