Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000363780 | SCV000430673 | uncertain significance | Cystinuria | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| ARUP Laboratories, |
RCV000756651 | SCV000884531 | uncertain significance | not provided | 2018-02-08 | criteria provided, single submitter | clinical testing | The SLC3A1 p.Arg504Cys variant (rs201143887), to our knowledge, is not reported in the medical literature, but it is reported in ClinVar (Variation ID: 336207). This variant is also found in the non-Finnish European population with an allele frequency of 0.016% (20/126,482 alleles) in the Genome Aggregation Database. The arginine at codon 504 is weakly conserved considering 21 species (Alamut software v2.10.0), and computational analyses predict that this variant does not affect the structure/function of the SLC3A1 protein (SIFT: tolerated, PolyPhen2: benign). However, based on the available information, the clinical significance of the p.Arg504Cys variant is uncertain at this time. |
| Invitae | RCV000363780 | SCV003255802 | uncertain significance | Cystinuria | 2024-01-22 | 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 504 of the SLC3A1 protein (p.Arg504Cys). This variant is present in population databases (rs201143887, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SLC3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 336207). 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) has been performed at Invitae 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 SLC3A1 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. |