ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1106A>G (p.Tyr369Cys)

dbSNP: rs786202218
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164934 SCV000215623 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-10 criteria provided, single submitter clinical testing The p.Y369C variant (also known as c.1106A>G), located in coding exon 7 of the BRIP1 gene, results from an A to G substitution at nucleotide position 1106. The tyrosine at codon 369 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Counsyl RCV000411336 SCV000489897 uncertain significance Fanconi anemia complementation group J 2016-07-18 criteria provided, single submitter clinical testing
Counsyl RCV000409363 SCV000489898 uncertain significance Ovarian neoplasm 2016-07-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000526617 SCV000633533 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-12-12 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 369 of the BRIP1 protein (p.Tyr369Cys). This variant is present in population databases (rs786202218, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 185494). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRIP1 protein function. 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 Diagnostics, LLC DBA Color Health RCV000164934 SCV000684111 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-21 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 369 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 hereditary cancer in the literature. This variant has been identified in 1/251304 chromosomes 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.
Myriad Genetics, Inc. RCV003316032 SCV004019394 uncertain significance Familial cancer of breast 2023-02-28 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
GeneDx RCV003322755 SCV004028356 uncertain significance not provided 2023-08-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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