ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2608G>C (p.Ala870Pro)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001206620 SCV001377936 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-09-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 870 of the BRCA1 protein (p.Ala870Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with breast cancer (PMID: 20104584). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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.
Integrated Genetics/Laboratory Corporation of America RCV001255590 SCV001432092 uncertain significance not specified 2020-08-10 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2608G>C (p.Ala870Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251122 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2608G>C has been reported in the literature in at-least one individual affected with Contralateral Breast Cancer (example, Borg_2010, Capanu_2011). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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