Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000195388 | SCV000075515 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-11-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000132145 | SCV000187216 | likely benign | Hereditary cancer-predisposing syndrome | 2019-01-17 | 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 |
RCV000047502 | SCV000210103 | uncertain significance | not provided | 2020-10-30 | criteria provided, single submitter | clinical testing | Observed in at least one individual with ovarian cancer (Alsop 2012); Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as c.1627A>G; This variant is associated with the following publications: (PMID: 15235020, 16267036, 22711857, 16518693, 23704879, 31131967) |
| Counsyl | RCV000111633 | SCV000785209 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-06-02 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000132145 | SCV000909379 | likely benign | Hereditary cancer-predisposing syndrome | 2018-01-25 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780972 | SCV000918673 | uncertain significance | not specified | 2017-10-23 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA1 c.1508A>G (p.Lys503Arg) variant involves the alteration of a non-conserved nucleotide located in the BRCA1 nuclear localization signal 1 (NLS1) (Fabbro 2002). 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). One study based on evolutionary comparative analyses predicted a benign role of the variant (Burk-Herrick 2005), although functional studies have not confirmed this prediction. This variant was found in 3/245882 control chromosomes (gnomAD) at a frequency of 0.0000122, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). The variant was observed in at least one individual with ovarian cancer (Alsop 2012) and also has been reported in affected individual(s) from HBOC families (Judkins 2005), however limited information was provided (i.e. no co-segregation data were included) so the causal link between the variant and disease could not be independently validated. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS, until additional information becomes available. |
| University of Washington Department of Laboratory Medicine, |
RCV000132145 | SCV003851249 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| Breast Cancer Information Core |
RCV000111633 | SCV000144115 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-02-20 | no assertion criteria provided | clinical testing |