Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000166710 | SCV000217520 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-02 | criteria provided, single submitter | clinical testing | The p.P315L variant (also known as c.944C>T), located in coding exon 4 of the BARD1 gene, results from a C to T substitution at nucleotide position 944. The proline at codon 315 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well 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. |
Labcorp Genetics |
RCV000469087 | SCV000545604 | uncertain significance | Familial cancer of breast | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 315 of the BARD1 protein (p.Pro315Leu). This variant is present in population databases (rs148760338, gnomAD 0.003%). 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: 187028). 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 leucine 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. |
Color Diagnostics, |
RCV000166710 | SCV000682826 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-05 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 315 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 6/250798 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. |
Counsyl | RCV000469087 | SCV000785017 | uncertain significance | Familial cancer of breast | 2017-03-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001589038 | SCV001814638 | uncertain significance | not provided | 2019-12-03 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
MGZ Medical Genetics Center | RCV000469087 | SCV002581311 | uncertain significance | Familial cancer of breast | 2022-01-31 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000469087 | SCV004019285 | uncertain significance | Familial cancer of breast | 2023-02-24 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Baylor Genetics | RCV000469087 | SCV004214984 | uncertain significance | Familial cancer of breast | 2023-09-30 | criteria provided, single submitter | clinical testing |