Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219768 | SCV000276551 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-06-27 | criteria provided, single submitter | clinical testing | The c.838_839delTT pathogenic mutation, located in coding exon 4 of the BARD1 gene, results from a deletion of two nucleotides at nucleotide positions 838 to 839, causing a translational frameshift with a predicted alternate stop codon (p.L280Tfs*4). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Gene |
RCV000657368 | SCV000779100 | pathogenic | not provided | 2017-08-03 | criteria provided, single submitter | clinical testing | This deletion of two nucleotides in BARD1 is denoted c.838_839delTT at the cDNA level and p.Leu280ThrfsX4 (L280TfsX4) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CTCT[delTT]ACCA. The deletion causes a frameshift which changes a Leucine to a Threonine at codon 280, and creates a premature stop codon at position 4 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through protein truncation. We consider this variant to be pathogenic. |
| Labcorp Genetics |
RCV001204956 | SCV001376188 | pathogenic | Familial cancer of breast | 2025-01-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu280Thrfs*4) 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 variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 232418). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV001204956 | SCV004043334 | pathogenic | Familial cancer of breast | 2023-05-19 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV001204956 | SCV004217285 | likely pathogenic | Familial cancer of breast | 2024-03-28 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000657368 | SCV005625687 | likely pathogenic | not provided | 2024-02-16 | criteria provided, single submitter | clinical testing | The BARD1 c.838_839del (p.Leu280Thrfs*4) variant has not been reported in individuals with BARD1-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic. |