ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1898C>T (p.Pro633Leu) (rs398122647)

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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 RCV000129651 SCV000184449 uncertain significance Hereditary cancer-predisposing syndrome 2015-02-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000129651 SCV000912046 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-12 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000509321 SCV000607248 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Integrated Genetics/Laboratory Corporation of America RCV000509321 SCV000698896 uncertain significance not provided 2016-10-24 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1898C>T (p.Pro633Leu) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 1/121302 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; 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.
Invitae RCV000637600 SCV000759066 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-25 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 633 of the BRCA1 protein (p.Pro633Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs398122647, ExAC 0.009%). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 91568). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000505826 SCV000296412 uncertain significance not specified 2017-05-05 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077085 SCV000108882 uncertain significance Breast-ovarian cancer, familial 1 2008-12-29 no assertion criteria provided clinical testing

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