Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985418 | SCV001133587 | uncertain significance | not provided | 2023-02-02 | criteria provided, single submitter | clinical testing | It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported to cause the complete skipping of exon 14 and a truncated protein product (PMID: 31143303 (2019)). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant may affect proper BRCA1 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant. |
| Invitae | RCV003645120 | SCV004535601 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-05-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 13 and introduces a premature termination codon (PMID: 31143303; Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 801077). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 13 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. |