Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001300720 | SCV001489869 | uncertain significance | Long QT syndrome | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 419 of the SNTA1 protein (p.Arg419Cys). This variant is present in population databases (rs375515058, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SNTA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 809246). 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 SNTA1 protein function with a negative predictive value of 80%. 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. |
| ARUP Laboratories, |
RCV001803192 | SCV002048409 | uncertain significance | Long QT syndrome 12 | 2020-10-01 | criteria provided, single submitter | clinical testing | The SNTA1 c.1255C>T; p.Arg419Cys variant (rs375515058), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 809246). This variant is found on only three chromosomes (3/251062 alleles) in the Genome Aggregation Database. The arginine at codon 419 is moderately conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.Arg419Cys variant is uncertain at this time. |