Submissions for variant NM_032043.3(BRIP1):c.3406C>T (p.Leu1136Phe)

dbSNP: rs1555572626

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000579866	SCV000684260	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with phenylalanine at codon 1136 of the BRIP1 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 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000636184	SCV000757616	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2022-12-17	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1136 of the BRIP1 protein (p.Leu1136Phe). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 489833). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics	RCV000579866	SCV002618399	uncertain significance	Hereditary cancer-predisposing syndrome	2021-06-13	criteria provided, single submitter	clinical testing	The p.L1136F variant (also known as c.3406C>T), located in coding exon 19 of the BRIP1 gene, results from a C to T substitution at nucleotide position 3406. The leucine at codon 1136 is replaced by phenylalanine, an amino acid with highly similar 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.