Submissions for variant NM_000059.4(BRCA2):c.4142A>C (p.Lys1381Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV004602344	SCV005102184	uncertain significance	Hereditary cancer-predisposing syndrome	2024-04-22	criteria provided, single submitter	clinical testing	The p.K1381T variant (also known as c.4142A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 4142. The lysine at codon 1381 is replaced by threonine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health	RCV004805131	SCV005424421	uncertain significance	BRCA2-related cancer predisposition	2024-02-22	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with threonine at codon 1381 of the BRCA2 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 BRCA2-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.