ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2993T>G (p.Leu998Arg)

dbSNP: rs1567793330
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000803204 SCV000943066 uncertain significance Hereditary breast ovarian cancer syndrome 2020-12-31 criteria provided, single submitter clinical testing 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 998 of the BRCA1 protein (p.Leu998Arg). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and arginine.
Color Diagnostics, LLC DBA Color Health RCV001175762 SCV001339474 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV001175762 SCV002750710 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-14 criteria provided, single submitter clinical testing The p.L998R variant (also known as c.2993T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 2993. The leucine at codon 998 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV001175762 SCV003849204 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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