ClinVar Miner

Submissions for variant NM_000038.6(APC):c.14C>T (p.Ser5Leu) (rs373718658)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229070 SCV000282698 uncertain significance Familial adenomatous polyposis 1 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 5 of the APC protein (p.Ser5Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs373718658, ExAC 0.002%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 236561). 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 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 RCV000589294 SCV000693999 uncertain significance not provided 2017-02-09 criteria provided, single submitter clinical testing Variant summary: The APC c.14C>T (p.Ser5Leu) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 1/121200 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714). 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. One clinical diagnostic laboratory classified this variant as uncertain significance. 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.
Color RCV000775115 SCV000909223 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-23 criteria provided, single submitter clinical testing

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