Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159508 | SCV000209462 | uncertain significance | not provided | 2014-10-06 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.974A>G at the cDNA level, p.His325Arg (H325R) at the protein level, and results in the change of a Histidine to an Arginine (CAT>CGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC His325Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Histidine and Arginine share similar properties, this is considered a conservative amino acid substitution. APC His325Arg occurs at a position that is highly conserved across species and is located in a Leu-rich region with specific function unknown (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether APC His325Arg is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Invitae | RCV003743591 | SCV002267340 | uncertain significance | Familial adenomatous polyposis 1 | 2021-11-29 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with APC-related conditions. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 181767). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 325 of the APC protein (p.His325Arg). |