Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588472 | SCV000699300 | pathogenic | Hereditary breast ovarian cancer syndrome | 2017-06-16 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA1 c.754delC (p.Arg252Valfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.783T>G [p.Tyr261X], c.784delC [p.Gln262fs). The variant has been identified in at least two patients with triple-negative breast cancer (Lang_BRCA1&2_IJC_2017; Yang_PLoS One_2015) and is absent from the large control database ExAC and control cohorts reported in the literature (0/122396 control chromosomes). One in silico tool predicts a damaging outcome for this variant. Taken together, this variant is classified as pathogenic. |
Invitae | RCV000588472 | SCV000758912 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-12-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg252Valfs*46) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer syndrome (PMID: 25927356). ClinVar contains an entry for this variant (Variation ID: 496401). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002395510 | SCV002674053 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-05-30 | criteria provided, single submitter | clinical testing | The c.754delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 754, causing a translational frameshift with a predicted alternate stop codon. This pathogenic mutation has been reported in a Chinese individual diagnosed with breast cancer at age 35 (Yang X et al. PLoS ONE, 2015 Apr;10:e0125571). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |