Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000119182 | SCV000153918 | uncertain significance | Familial adenomatous polyposis 1 | 2018-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 230 of the APC protein (p.Arg230His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs587780545, ExAC 0.02%). This variant has been reported in an individual with colon cancer (PMID: 28125075). ClinVar contains an entry for this variant (Variation ID: 132732). 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. |
| Color | RCV000579594 | SCV000681832 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-01 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV000589003 | SCV000694102 | uncertain significance | not provided | 2016-09-02 | criteria provided, single submitter | clinical testing | Variant summary: The APC c.689G>A (p.Arg230His) variant involves the alteration of a conserved nucleotide. Arg230 is conserved through species and located in the Adenomatous polyposis coli protein domain (InterPro). 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 8/120512 control chromosomes at a frequency of 0.0000664, which does not exceed the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714). 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 and/or reputable databases/clinical diagnostic laboratories; 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. |