Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000525601 | SCV000636017 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-11-23 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this variant does not affect mRNA splicing (PMID: 30209399). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 462664). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 18 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein, but it affects a nucleotide within the consensus splice site of the intron. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797748 | SCV002041732 | uncertain significance | not specified | 2021-11-24 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.5193+6T>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Although 4/4 computational tools predict no significant impact on normal splicing, these predictions have yet to be confirmed by functional studies. The variant was absent in 251034 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5193+6T>C in individuals affected with Hereditary Breast and Ovarian Cancer Syndrome has been reported. One functional study reported experimental evidence evaluating an impact on protein function and showed no damaging effect of this variant in homology directed repair (HDR) activity (Findlay_2018). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS. |
| Brotman Baty Institute, |
RCV001072462 | SCV001237850 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |