Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000022350 | SCV001392118 | pathogenic | Renal carnitine transport defect | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp275*) in the SLC22A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC22A5 are known to be pathogenic (PMID: 9916797). This variant is present in population databases (rs386134207, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with primary carnitine deficiency (PMID: 15714519). ClinVar contains an entry for this variant (Variation ID: 25397). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000022350 | SCV003844977 | likely pathogenic | Renal carnitine transport defect | 2023-02-19 | criteria provided, single submitter | clinical testing | Variant summary: SLC22A5 c.825G>A (p.Trp275X) 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 8e-06 in 251484 control chromosomes (gnomAD). c.825G>A has been reported in the literature in individuals affected with Systemic Primary Carnitine Deficiency (examples: Dobrowolski_2005 and Gallant_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Gene |
RCV003229802 | SCV003927487 | pathogenic | not provided | 2023-05-23 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 32778825, 15714519, 28711408) |
| Baylor Genetics | RCV000022350 | SCV004201306 | pathogenic | Renal carnitine transport defect | 2023-07-10 | criteria provided, single submitter | clinical testing |