Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003651853 | SCV000552539 | uncertain significance | Familial adenomatous polyposis 1 | 2022-09-05 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 411398). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs773087899, gnomAD 0.0009%). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 444 of the APC protein (p.His444Gln). |
Ambry Genetics | RCV002383828 | SCV002693089 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-29 | criteria provided, single submitter | clinical testing | The p.H444Q variant (also known as c.1332T>G), located in coding exon 10 of the APC gene, results from a T to G substitution at nucleotide position 1332. The histidine at codon 444 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |