Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000112693 | SCV000300276 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Invitae | RCV000049034 | SCV000077047 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-02-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This truncation is expected to partially remove the C-terminal BRCT domain of BRCA1 protein, which is important for DNA repair activity (PMID: 14576433, 15133503). A different deleterious variant p.Tyr1853* located downstream of this variant has been shown to disrupt BRCA1 protein function (PMID: 8942979, 20681793, 10811118, 11256609, 17308087), suggesting that although this particular variant may not result in nonsense mediated decay, it is expected to affect BRCA1 protein function. This variant has been reported in individuals affected with breast cancer (PMID: 9544766, 16835750, 21614564, 27393621). This variant is also known as 5640delA in the literature. ClinVar contains an entry for this variant (Variation ID: 55612). This variant is not present in population databases (ExAC no frequency). This sequence change deletes 1 nucleotide in exon 23 of the BRCA1 mRNA (c.5521delA), causing a frameshift at codon 1841. This creates a premature translational stop signal in the last exon of the BRCA1 mRNA (p.Ser1841Valfs*2). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated protein by eliminating 22 amino acid residues from the full-length BRCA1 protein. |
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000112693 | SCV000326351 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000564883 | SCV000661000 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-29 | criteria provided, single submitter | clinical testing | The c.5521delA pathogenic mutation, located in coding exon 22 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 5521, causing a translational frameshift with a predicted alternate stop codon (p.S1841Vfs*2). This alteration occurs at the 3' terminus of theBRCA1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 22 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This alteration was detected in a cohort of women diagnosed with breast cancer (Malone KE, JAMA 1998 Mar;279(12):922-9). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Breast Cancer Information Core |
RCV000112693 | SCV000145565 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 1999-04-06 | no assertion criteria provided | clinical testing |