ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1825A>G (p.Thr609Ala) (rs189758577)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000528910 SCV000633576 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-08-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 609 of the BRIP1 protein (p.Thr609Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Color RCV000581727 SCV000689285 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590700 SCV000699676 uncertain significance not provided 2017-05-22 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.1825A>G (p.Thr609Ala) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 121328 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.

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