Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000022323 | SCV000829524 | pathogenic | Renal carnitine transport defect | 2025-01-30 | criteria provided, single submitter | clinical testing | This sequence change affects codon 151 of the SLC22A5 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SLC22A5 protein. This variant is present in population databases (rs386134194, gnomAD 0.009%). This variant has been observed in individual(s) with primary carnitine deficiency (PMID: 28841266; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 25375). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Mendelics | RCV000022323 | SCV001136972 | pathogenic | Renal carnitine transport defect | 2023-03-24 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000022323 | SCV002055747 | uncertain significance | Renal carnitine transport defect | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000022323 | SCV004201252 | likely pathogenic | Renal carnitine transport defect | 2024-02-29 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000022323 | SCV005669197 | likely pathogenic | Renal carnitine transport defect | 2024-04-16 | criteria provided, single submitter | clinical testing | |
Clinical Genomics Laboratory, |
RCV000022323 | SCV001427024 | uncertain significance | Renal carnitine transport defect | 2019-01-10 | no assertion criteria provided | clinical testing | The p.Val151= variant in the SLC22A5 gene has been seen previously in 3 individuals with primary systemic carnitine deficiency (unpublished, ARUP Primary Carnitine Deficiency and SLC22A5 Database). In two of these patients, a second likely pathogenic/pathogenic variant was identified [Thr440Met; Pro46Ser], consistent with autosomal recessive inheritence. The p.Val151= variant has been identified in 11/129200 non-Finnish European alleles by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Computational splicing tools predict formation of a cryptic splice site; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Val151= variant is uncertain. However, there is suspicion that this variant could be associated with primary systemic carnitine deficiency as it has been seen in 3 other affected individuals. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2, PM3, PP3] |