ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5465T>G (p.Val1822Gly) (rs459552)

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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 RCV000216852 SCV000274821 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000471267 SCV000552445 uncertain significance Familial adenomatous polyposis 1 2016-07-28 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 1822 of the APC protein (p.Val1822Gly). The valine residue is weakly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a APC-related disease. ClinVar contains an entry for this variant (Variation ID: 231079). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000589084 SCV000694079 uncertain significance not provided 2016-12-09 criteria provided, single submitter clinical testing Variant summary: The APC c.5465T>G (p.Val1822Gly) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 120944 control chromosomes. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. 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. 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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