Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164187 | SCV000214807 | likely benign | Hereditary cancer-predisposing syndrome | 2018-12-19 | 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. |
| Gene |
RCV000481606 | SCV000570480 | uncertain significance | not provided | 2023-05-03 | 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; Published functional studies demonstrate homology directed-repair activity and cell survival comparable to wild-type, but reduced protein expression and single-strand annealing activity (Towler et al., 2013; Starita et al., 2018; Billaud et al., 2021); Also known as 691T>A; This variant is associated with the following publications: (PMID: 15385441, 23161852, 31131967, 30219179, 9788437, 20215511, 34749799, 37090572, 29884841, 27535533, 32377563) |
| Color Diagnostics, |
RCV000164187 | SCV000905043 | likely benign | Hereditary cancer-predisposing syndrome | 2016-01-14 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000779902 | SCV000916804 | uncertain significance | not specified | 2018-09-25 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.572T>A (p.Val191Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 246176 control chromosomes (gnomAD). To our knowledge, no occurrence of c.572T>A in individuals affected with Hereditary Breast and Ovarian Cancer has been reported. A functional study, Towler_2013, found the variant to act comparable to wild type in HDR activity. However, the SSA activity was significantly decreased (~40% of WT activity), although the protein expression was also reduced. Two ClinVar submission from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance and likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Invitae | RCV001343980 | SCV001538006 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-07-06 | criteria provided, single submitter | clinical testing | |
| Breast Cancer Information Core |
RCV000112745 | SCV000145631 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing |