ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4301A>T (p.Lys1434Ile) (rs397507714)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044389 SCV000072402 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces lysine with isoleucine at codon 1434 of the BRCA2 protein (p.Lys1434Ile). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast and/or ovarian cancer and pancreatic cancer (PMID: 16683254, 25356972). This variant is also known as 4529A>T in the literature. ClinVar contains an entry for this variant (Variation ID: 51628). Based on a multifactorial likelihood algorithm using genetic, in silico, and statistical data, this variant has been determined to have a low probability of being pathogenic (PMID: 21990134). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
Ambry Genetics RCV000131680 SCV000186716 likely benign Hereditary cancer-predisposing syndrome 2017-06-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with mutation in same gene (phase unknown),Other data supporting benign classification
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506062 SCV000600582 uncertain significance not specified 2016-11-22 criteria provided, single submitter clinical testing
Color RCV000131680 SCV000688867 likely benign Hereditary cancer-predisposing syndrome 2017-05-04 criteria provided, single submitter clinical testing

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