Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002445899 | SCV002677793 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-25 | criteria provided, single submitter | clinical testing | The p.H281R variant (also known as c.842A>G), located in coding exon 6 of the BRIP1 gene, results from an A to G substitution at nucleotide position 842. The histidine at codon 281 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003099940 | SCV003504714 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-04-26 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 281 of the BRIP1 protein (p.His281Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Baylor Genetics | RCV003464494 | SCV004214787 | uncertain significance | Familial cancer of breast | 2023-08-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV004765490 | SCV005377908 | uncertain significance | not provided | 2023-10-25 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |