ClinVar Miner

Submissions for variant NM_000038.6(APC):c.437C>T (p.Ala146Val) (rs1305794169)

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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 RCV000566219 SCV000667743 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000700936 SCV000829714 uncertain significance Familial adenomatous polyposis 1 2018-08-20 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 146 of the APC protein (p.Ala146Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 482475). 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: "Possibly 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 RCV000780845 SCV000918455 uncertain significance not specified 2017-10-26 criteria provided, single submitter clinical testing Variant summary: The APC c.437C>T (p.Ala146Val) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 240486 control chromosomes. The variant has been reported in a breast cancer patient without strong evidence for or against pathogenicity. Taken together, this variant is classified as VUS.

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