Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001851731 | SCV002168440 | uncertain significance | not provided | 2023-05-12 | 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 not expected to disrupt ATIC protein function. ClinVar contains an entry for this variant (Variation ID: 7810). This missense change has been observed in individual(s) with clinical features of AICA-ribosiduria and complex congenital heart defects (PMID: 15114530, 28991257, 32557644). This variant is present in population databases (rs121434478, gnomAD 0.004%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 426 of the ATIC protein (p.Lys426Arg). Experimental studies have shown that this missense change affects ATIC function (PMID: 15114530). 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. |
Institute of Human Genetics, |
RCV002287326 | SCV002578106 | likely pathogenic | Macular dystrophy | 2021-12-08 | criteria provided, single submitter | clinical testing | ACMG categories: PM1,PM2,PP3,PP5 |
OMIM | RCV000008253 | SCV000028460 | pathogenic | AICA-ribosiduria | 2004-06-01 | no assertion criteria provided | literature only |