Submissions for variant NM_007294.4(BRCA1):c.2434A>G (p.Lys812Glu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002459915	SCV002737208	uncertain significance	Hereditary cancer-predisposing syndrome	2024-03-10	criteria provided, single submitter	clinical testing	The p.K812E variant (also known as c.2434A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 2434. The lysine at codon 812 is replaced by glutamic acid, an amino acid with similar properties. This alteration was not observed in 7,051 unselected female breast cancer patients and was observed with an allele frequency of 0.00009 in 11,241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). 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.
University of Washington Department of Laboratory Medicine, University of Washington	RCV002459915	SCV003847670	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).