ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3944C>G (p.Pro1315Arg) (rs80357500)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131512 SCV000186505 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000131512 SCV000688458 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-11 criteria provided, single submitter clinical testing
Counsyl RCV000083042 SCV000786126 uncertain significance Breast-ovarian cancer, familial 1 2018-02-28 criteria provided, single submitter clinical testing
GeneDx RCV000424747 SCV000528363 likely benign not specified 2017-08-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000586746 SCV000699087 uncertain significance not provided 2017-05-26 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3944C>G (p.Pro1315Arg) variant involves the alteration of a non-conserved nucleotide, resulting in a missense substitution that does not lie within a known functional domain (InterPro). 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent from the large control database ExAC (0/121400 control chromosomes). Multiple clinical diagnostic laboratories/reputable databases have classified this variant with conflicting interpretations, including uncertain significance and likely benign. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor has it been 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.
Invitae RCV000469729 SCV000549277 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-21 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 1315 of the BRCA1 protein (p.Pro1315Arg). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 96921). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000083042 SCV000267707 uncertain significance Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083042 SCV000115116 likely benign Breast-ovarian cancer, familial 1 2011-02-10 no assertion criteria provided clinical testing

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