Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000074886 | SCV000108099 | no known pathogenicity | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | MAF >1% |
Ambry Genetics | RCV000162507 | SCV000212898 | likely benign | Hereditary cancer-predisposing syndrome | 2012-11-06 | 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. |
Color Diagnostics, |
RCV000162507 | SCV000690369 | benign | Hereditary cancer-predisposing syndrome | 2022-01-02 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000584641 | SCV001360589 | benign | not specified | 2019-02-07 | criteria provided, single submitter | clinical testing | Variant summary: MSH6 c.3557-4dupT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.15 in 27938 control chromosomes in the gnomAD database, including 314 homozygotes. The observed variant frequency is approximately 1075 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. c.3557-4dupT has been reported in the literature in multiple affected individuals and also, a large number of controls and has been described as a polymorphism (Wasielewski_2010, Vahteristo_2005, Charames_2000). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. |
Gene |
RCV001689613 | SCV001910578 | benign | not provided | 2019-11-19 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000162507 | SCV002528044 | benign | Hereditary cancer-predisposing syndrome | 2022-01-06 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000584641 | SCV002552349 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002477212 | SCV002798704 | likely benign | Endometrial carcinoma; Lynch syndrome 5; Mismatch repair cancer syndrome 3 | 2022-05-13 | criteria provided, single submitter | clinical testing | |
Unidad de Genómica Garrahan, |
RCV000584641 | SCV004233763 | benign | not specified | 2024-01-24 | criteria provided, single submitter | clinical testing | This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. |
Mayo Clinic Laboratories, |
RCV000584641 | SCV000691940 | benign | not specified | no assertion criteria provided | clinical testing | ||
Diagnostic Laboratory, |
RCV000613784 | SCV000734221 | benign | Lynch syndrome 5 | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000584641 | SCV001800145 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000584641 | SCV001905989 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000584641 | SCV001921387 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000584641 | SCV001926798 | benign | not specified | no assertion criteria provided | clinical testing |