Submissions for variant NM_032043.3(BRIP1):c.1556T>A (p.Ile519Asn)

dbSNP: rs1555603538

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000581012	SCV000684139	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with asparagine at codon 519 of the BRIP1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRIP1-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.
Ambry Genetics	RCV000581012	SCV002708848	uncertain significance	Hereditary cancer-predisposing syndrome	2022-07-26	criteria provided, single submitter	clinical testing	The p.I519N variant (also known as c.1556T>A), located in coding exon 10 of the BRIP1 gene, results from a T to A substitution at nucleotide position 1556. The isoleucine at codon 519 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is conserved. 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.