Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001939569 | SCV002227771 | pathogenic | Salla disease | 2023-10-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp246*) in the SLC17A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC17A5 are known to be pathogenic (PMID: 10581036, 10947946, 15172001). This variant is present in population databases (rs755923873, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SLC17A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1454733). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001939569 | SCV002572180 | likely pathogenic | Salla disease | 2022-08-19 | criteria provided, single submitter | clinical testing | Variant summary: SLC17A5 c.738G>A (p.Trp246X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 248260 control chromosomes (gnomAD). To our knowledge, no occurrence of c.738G>A in individuals affected with Sialic Acid Storage Disorder and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Prevention |
RCV004538684 | SCV004121469 | likely pathogenic | SLC17A5-related disorder | 2023-03-11 | criteria provided, single submitter | clinical testing | The SLC17A5 c.738G>A variant is predicted to result in premature protein termination (p.Trp246*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00089% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-74345186-C-T). Nonsense variants in SLC17A5 are expected to be pathogenic, and therefore we interpret c.738G>A (p.Trp246*) as likely pathogenic. |
| Baylor Genetics | RCV001939569 | SCV004201233 | likely pathogenic | Salla disease | 2022-10-18 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005032003 | SCV005672828 | likely pathogenic | Sialic acid storage disease, severe infantile type; Salla disease | 2024-02-09 | criteria provided, single submitter | clinical testing |