Submissions for variant NM_007294.4(BRCA1):c.2490G>T (p.Lys830Asn)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002430937	SCV002741815	uncertain significance	Hereditary cancer-predisposing syndrome	2022-10-31	criteria provided, single submitter	clinical testing	The p.K830N variant (also known as c.2490G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 2490. The lysine at codon 830 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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	RCV002430937	SCV003847626	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).
All of Us Research Program, National Institutes of Health	RCV004804478	SCV005428564	uncertain significance	BRCA1-related cancer predisposition	2024-06-09	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with asparagine at codon 830 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders 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.