Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131972 | SCV000187030 | likely benign | Hereditary cancer-predisposing syndrome | 2018-07-21 | 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 |
RCV000588317 | SCV000209945 | likely benign | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 9010228) |
| Invitae | RCV001088847 | SCV000549295 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-15 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000131972 | SCV000688399 | likely benign | Hereditary cancer-predisposing syndrome | 2017-07-17 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002228071 | SCV000698976 | likely benign | not specified | 2023-07-11 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.2735A>G (p.Lys912Arg) results in a 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 4.4e-05 in 250742 control chromosomes, predominantly at a frequency of 0.00032 (i.e., 11 heterozygotes) within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome (4.4e-05 vs 0.001), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.2735A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Six submitters have reported clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and a predominant consensus as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000588317 | SCV002047289 | likely benign | not provided | 2023-04-24 | criteria provided, single submitter | clinical testing | |
| University of Washington Department of Laboratory Medicine, |
RCV000131972 | SCV003849393 | 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). |
| Sharing Clinical Reports Project |
RCV000031068 | SCV000053664 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2011-11-04 | no assertion criteria provided | clinical testing |