ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4377A>T (p.Lys1459Asn)

dbSNP: rs2052743174
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001224284 SCV001396472 uncertain significance Hereditary breast ovarian cancer syndrome 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 1459 of the BRCA1 protein (p.Lys1459Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine 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, LLC DBA Color Health RCV003584860 SCV004360182 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-16 criteria provided, single submitter clinical testing This missense variant replaces lysine with asparagine at codon 1459 of the BRCA1 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 not been identified 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.

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