Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001266566 | SCV001444742 | uncertain significance | Inborn genetic diseases | 2020-02-25 | criteria provided, single submitter | clinical testing | The alteration results in an amino acid change:_x000D_ _x000D_ The c.14486G>A (p.R4829H) alteration is located in coding exon 77 of the HERC1 gene. This alteration results from a G to A substitution at nucleotide position 14486, causing the arginine (R) at amino acid position 4829 to be replaced by a histidine (H). The alteration is rare in population databases: _x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the c.14486G>A alteration was observed in 0.001% (4/279406) of total alleles studied. The altered amino acid is conserved throughout evolution:_x000D_ _x000D_ The R4829 amino acid is conserved in available vertebrate species. in silico prediction is inconclusive:_x000D_ _x000D_ The in silico prediction for the R4829H alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV002541627 | SCV002967050 | uncertain significance | not provided | 2022-10-12 | criteria provided, single submitter | clinical testing | 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 expected to disrupt HERC1 protein function. ClinVar contains an entry for this variant (Variation ID: 985584). This variant has not been reported in the literature in individuals affected with HERC1-related conditions. This variant is present in population databases (rs374249242, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 4829 of the HERC1 protein (p.Arg4829His). 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. |
| Gene |
RCV002541627 | SCV005421455 | likely pathogenic | not provided | 2024-06-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD) |