ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4384G>A (p.Glu1462Lys)

gnomAD frequency: 0.00001  dbSNP: rs141255461
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000174571 SCV000225891 uncertain significance not provided 2014-08-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000637603 SCV000759069 uncertain significance Hereditary breast ovarian cancer syndrome 2023-06-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1462 of the BRCA1 protein (p.Glu1462Lys). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 194244). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency).
Color Diagnostics, LLC DBA Color Health RCV000774943 SCV000909028 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-06 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1462 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.
Ambry Genetics RCV000774943 SCV001184125 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-11 criteria provided, single submitter clinical testing The p.E1462K variant (also known as c.4384G>A), located in coding exon 12 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4384. The glutamic acid at codon 1462 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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.
Fulgent Genetics, Fulgent Genetics RCV002492736 SCV002780020 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S 2021-07-21 criteria provided, single submitter clinical testing

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