Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486296 | SCV000567370 | uncertain significance | not provided | 2015-07-16 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.3656C>A at the cDNA level, p.Ser1219Tyr (S1219Y) at the protein level, and results in the change of a Serine to a Tyrosine (TCC>TAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ser1219Tyr 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 Serine and Tyrosine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Ser1219Tyr occurs at a position not conserved and is within a serine rich region as well as the region responsible for down-regulation through a process mediated by direct ubiquitination (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 Ser1219Tyr is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Invitae | RCV003651923 | SCV001378153 | uncertain significance | Familial adenomatous polyposis 1 | 2019-06-30 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with tyrosine at codon 1219 of the APC protein (p.Ser1219Tyr). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tyrosine. This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 419520). 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"). |