Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586621 | SCV000694132 | uncertain significance | not provided | 2017-06-23 | criteria provided, single submitter | clinical testing | Variant summary: The APC c.800G>C (p.Gly267Ala) variant involves the alteration of a conserved nucleotide, resulting in a missense change within the pyridoxal phosphate-dependent transferase, major region, subdomain 1 (InterPro). 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to non-functioning tool). This variant is absent from the large database ExAC (0/120038 control chromosomes). To our knowledge, the variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor has it been 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. |
| Labcorp Genetics |
RCV004562639 | SCV001414462 | uncertain significance | Familial adenomatous polyposis 1 | 2019-11-11 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 495375). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with alanine at codon 267 of the APC protein (p.Gly267Ala). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and alanine. |