Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001022405 | SCV001184136 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-09-10 | criteria provided, single submitter | clinical testing | The p.W146* pathogenic mutation (also known as c.438G>A), located in coding exon 4 of the BARD1 gene, results from a G to A substitution at nucleotide position 438. This changes the amino acid from a tryptophan to a stop codon within coding exon 4. This alteration was detected in a cohort of 8085 consecutive unselected Chinese patients with breast cancer who underwent multi-gene panel testing (Sun J et al. Clin. Cancer Res., 2017 Oct;23:6113-6119). 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. |
Labcorp Genetics |
RCV001862215 | SCV002244715 | pathogenic | Familial cancer of breast | 2024-08-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp146*) in the BARD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BARD1 are known to be pathogenic (PMID: 20077502, 21344236). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 28724667). ClinVar contains an entry for this variant (Variation ID: 824854). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV001862215 | SCV004044184 | pathogenic | Familial cancer of breast | 2023-05-18 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
Baylor Genetics | RCV001862215 | SCV004217292 | pathogenic | Familial cancer of breast | 2023-03-24 | criteria provided, single submitter | clinical testing |