Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002012528 | SCV002279505 | uncertain significance | Mucopolysaccharidosis, MPS-II | 2024-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 317 of the IDS protein (p.Ala317Asp). This variant is present in population databases (rs374576277, gnomAD 0.006%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with IDS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1492947). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IDS 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. |
Ambry Genetics | RCV002370673 | SCV002688245 | uncertain significance | Inborn genetic diseases | 2022-06-14 | criteria provided, single submitter | clinical testing | The p.A317D variant (also known as c.950C>A), located in coding exon 7 of the IDS gene, results from a C to A substitution at nucleotide position 950. The alanine at codon 317 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |