Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000777553 | SCV000913416 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-26 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with asparagine at codon 1006 of the APC protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Gene |
RCV001775996 | SCV002012768 | uncertain significance | not provided | 2021-01-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV000777553 | SCV002754257 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-29 | criteria provided, single submitter | clinical testing | The p.H1006N variant (also known as c.3016C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 3016. The histidine at codon 1006 is replaced by asparagine, an amino acid with 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. |
Baylor Genetics | RCV003461046 | SCV004207814 | uncertain significance | Familial adenomatous polyposis 1 | 2023-06-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003535846 | SCV004266451 | uncertain significance | Familial adenomatous polyposis 1 | 2022-12-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 631365). 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. 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 asparagine, which is neutral and polar, at codon 1006 of the APC protein (p.His1006Asn). |