ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3700G>C (p.Val1234Leu) (rs763354142)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000197777 SCV000254979 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-05-16 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 1234 of the BRCA1 protein (p.Val1234Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. 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: 216664). 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.
Counsyl RCV000410498 SCV000488425 uncertain significance Breast-ovarian cancer, familial 1 2016-03-23 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508617 SCV000605840 uncertain significance not specified 2017-02-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509979 SCV000608211 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-22 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000508617 SCV000918695 uncertain significance not specified 2017-09-18 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3700G>C (p.Val1234Leu) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 121382 control chromosomes. 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 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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