Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000230578 | SCV000284888 | uncertain significance | Familial cancer of breast | 2023-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 336 of the BARD1 protein (p.Cys336Tyr). This variant is present in population databases (rs779527817, gnomAD 0.03%). 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: 237812). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV000561387 | SCV000668266 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-22 | criteria provided, single submitter | clinical testing | The p.C336Y variant (also known as c.1007G>A), located in coding exon 4 of the BARD1 gene, results from a G to A substitution at nucleotide position 1007. The cysteine at codon 336 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV000230578 | SCV000895392 | uncertain significance | Familial cancer of breast | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000561387 | SCV000911969 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-23 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with tyrosine at codon 336 of the BARD1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 6/251138 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298544 | SCV002598630 | uncertain significance | not specified | 2022-09-25 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003441808 | SCV004170587 | uncertain significance | not provided | 2023-11-10 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in 0/1229 biliary tract cancer cases and in at least 1/37583 controls (PMID: 36243179); This variant is associated with the following publications: (PMID: 15632137, 36243179) |
| Baylor Genetics | RCV000230578 | SCV004217171 | uncertain significance | Familial cancer of breast | 2023-09-06 | criteria provided, single submitter | clinical testing |