ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1958G>A (p.Arg653Lys) (rs1060503318)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491686 SCV000579851 likely pathogenic Hereditary cancer-predisposing syndrome 2016-12-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Rarity in general population databases (dbsnp, esp, 1000 genomes),Last nucleotide of exon,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Other data supporting pathogenic classification
Invitae RCV000646330 SCV000768098 pathogenic Familial adenomatous polyposis 1 2018-05-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 653 of the APC protein (p.Arg653Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant also falls at the last nucleotide of exon 15 of the APC coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with familial adenomatous polyposis and colorectal cancer (PMID: 20685668, 25590978, 18199528, 24599579). ClinVar contains an entry for this variant (Variation ID: 428128). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this missense change results in skipping of exon 15 (also known as exon 14 in the literature) (PMID: 20685668, 24599579). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759416 SCV000888725 likely pathogenic not provided 2018-04-06 criteria provided, single submitter clinical testing

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