Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001712292 | SCV000532691 | likely benign | not provided | 2019-06-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000554001 | SCV000644661 | benign | Tuberous sclerosis 2 | 2023-12-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000572855 | SCV000675575 | likely benign | Hereditary cancer-predisposing syndrome | 2019-01-23 | 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. |
Genome- |
RCV000554001 | SCV002041258 | benign | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797720 | SCV002041597 | likely benign | not specified | 2021-11-26 | criteria provided, single submitter | clinical testing | Variant summary: TSC2 c.721G>A (p.Val241Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 250168 control chromosomes (gnomAD v2.1 exomes dataset). This frequency is somewhat lower than the maximum expected for a pathogenic variant in TSC2 causing Tuberous Sclerosis Complex phenotype (6.9e-05), however in certain subpopulations the variant occurs with even higher allele frequencies, suggesting that it can be a benign polymorphism. To our knowledge, no occurrence of c.721G>A in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=1) / likely benign (n=2). Based on the evidence outlined above, the variant was classified as likely benign. |
Sema4, |
RCV000572855 | SCV002534100 | likely benign | Hereditary cancer-predisposing syndrome | 2021-06-27 | criteria provided, single submitter | curation |