Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000490909 | SCV000579792 | uncertain significance | Hereditary cancer-predisposing syndrome | 2013-12-12 | criteria provided, single submitter | clinical testing | ​The p.S835Y variant (also known as c.2504C>A) is located in coding exon 15 of the APC gene. This alteration results from a C to A substitution at nucleotide position 2504. The serine at codon 835 is replaced by tyrosine, an amino acid with dissimilar properties. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 7,600 alleles tested) in our clinical cohort (includes this individual). Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.S835Y remains unclear. |
| Invitae | RCV002231131 | SCV001509511 | uncertain significance | Familial adenomatous polyposis 1 | 2022-02-06 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 835 of the APC protein (p.Ser835Tyr). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 428103). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). |