Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159580 | SCV000209556 | uncertain significance | not provided | 2015-11-04 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.7892C>T at the cDNA level, p.Ser2631Phe (S2631F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCC>TTC). While this variant has been published as a somatic alteration it has not, to our knowledge, been published in the literature as either a germline pathogenic variant or a benign polymorphism (Minde 2011). APC Ser2631Phe 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 Phenylalanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Ser2631Phe occurs at a position that conserved through species and is located within the EB1 binding domain (Azzopardi 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether APC Ser2631Phe is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000572794 | SCV000672562 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | The p.S2631F variant (also known as c.7892C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 7892. The serine at codon 2631 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003650409 | SCV001210141 | uncertain significance | Familial adenomatous polyposis 1 | 2023-05-25 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs730881269, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 2631 of the APC protein (p.Ser2631Phe). ClinVar contains an entry for this variant (Variation ID: 181828). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. 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. |
Ce |
RCV000159580 | SCV001961896 | uncertain significance | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000159580 | SCV002011080 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000572794 | SCV002530933 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-23 | criteria provided, single submitter | curation |