ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1581G>C (p.Lys527Asn) (rs80357493)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132496 SCV000187590 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-21 criteria provided, single submitter clinical testing The p.K527N variant (also known as c.1581G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 1581. The lysine at codon 527 is replaced by asparagine, an amino acid with similar 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.
Color Health, Inc RCV000132496 SCV000911189 likely benign Hereditary cancer-predisposing syndrome 2015-11-25 criteria provided, single submitter clinical testing
Invitae RCV001313648 SCV001504152 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-02-27 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 527 of the BRCA1 protein (p.Lys527Asn). 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 with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 54300). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0. The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111650 SCV000144137 uncertain significance Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing

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