ClinVar Miner

Submissions for variant NM_003060.4(SLC22A5):c.235del (p.His79fs)

dbSNP: rs377767447
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000022306 SCV001403129 pathogenic Renal carnitine transport defect 2023-09-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.His79Thrfs*51) 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 (rs377767447, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with primary carnitine deficiency (PMID: 16652335). This variant is also known as c.232delC. ClinVar contains an entry for this variant (Variation ID: 25359).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000022306 SCV001482251 pathogenic Renal carnitine transport defect 2021-02-19 criteria provided, single submitter clinical testing Variant summary: SLC22A5 c.235delC (p.His79ThrfsX51) 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 1e-05 in 198962 control chromosomes (gnomAD). c.235delC has been reported in the literature in individuals affected with Systemic Primary Carnitine Deficiency (Amat di San Filippo_2006, Frigeni_2017). These data indicate that the variant may be associated with disease. Additionally, carnitine transport activity was measured in fibroblasts from one homozygous patient and the variant results in <10% of normal transport activity (Frigeni_2017). One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV000022306 SCV002055795 pathogenic Renal carnitine transport defect 2021-07-15 criteria provided, single submitter clinical testing

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