ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.3655A>C (p.Asn1219His)

dbSNP: rs1567727404
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000707033 SCV000836111 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2019-11-01 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 1219 of the BRIP1 protein (p.Asn1219His). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV001020812 SCV001182342 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-23 criteria provided, single submitter clinical testing The p.N1219H variant (also known as c.3655A>C), located in coding exon 19 of the BRIP1 gene, results from an A to C substitution at nucleotide position 3655. The asparagine at codon 1219 is replaced by histidine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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.

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