ClinVar Miner

Submissions for variant NM_000387.6(SLC25A20):c.532C>T (p.Arg178Ter)

gnomAD frequency: 0.00005  dbSNP: rs778220325
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657649 SCV000779396 pathogenic not provided 2019-12-06 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 a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 12801121, 25525159, 25614308, 15365988, 31980526, 31589614)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780710 SCV000918217 pathogenic Carnitine acylcarnitine translocase deficiency 2018-11-19 criteria provided, single submitter clinical testing Variant summary: SLC25A20 c.532C>T (p.Arg178X) 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. The variant allele was found at a frequency of 2.9e-05 in 277186 control chromosomes (gnbomAD). The variant, c.532C>T, has been reported in the literature in individuals affected with Carnitine-Acylcarnitine Translocase Deficiency (Vitoria_2014, Costa_2003). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000780710 SCV001237318 pathogenic Carnitine acylcarnitine translocase deficiency 2023-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg178*) in the SLC25A20 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC25A20 are known to be pathogenic (PMID: 25614308). This variant is present in population databases (rs778220325, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with carnitine acylcarnitine translocase deficiency (PMID: 12559850, 12801121, 25614308). ClinVar contains an entry for this variant (Variation ID: 545967). For these reasons, this variant has been classified as Pathogenic.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000657649 SCV002051639 pathogenic not provided 2021-03-12 criteria provided, single submitter clinical testing PVS1, PP4, PM2, PS4_supporting
Fulgent Genetics, Fulgent Genetics RCV000780710 SCV002780946 pathogenic Carnitine acylcarnitine translocase deficiency 2021-12-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000780710 SCV004201715 pathogenic Carnitine acylcarnitine translocase deficiency 2023-08-16 criteria provided, single submitter clinical testing

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