Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491729 | SCV000579854 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-03-04 | criteria provided, single submitter | clinical testing | The p.H2591D variant (also known as c.7771C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 7771. The histidine at codon 2591 is replaced by aspartic acid, an amino acid with similar 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. In the ESP, this variant was not observed in 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.005% (greater than 21000 alleles tested) in our clinical cohort. This amino acid position is moderately conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of p.H2591D remains unclear. |
| Labcorp Genetics |
RCV004564212 | SCV004502077 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-28 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 428129). 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). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 2591 of the APC protein (p.His2591Asp). |