Submissions for variant NM_000387.6(SLC25A20):c.804del (p.Phe269fs)

dbSNP: rs753414360

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000792302	SCV000931589	pathogenic	Carnitine acylcarnitine translocase deficiency	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe269Serfs*4) in the SLC25A20 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 33 amino acid(s) of the SLC25A20 protein. This variant is present in population databases (rs753414360, gnomAD 0.008%). This premature translational stop signal has been observed in individuals with carnitine-acylcarnitine translocase deficiency (PMID: 12559850, 21605995, 33634872, 35360862). This variant is also known as c.802delG. ClinVar contains an entry for this variant (Variation ID: 639496). This variant disrupts the C-terminus of the SLC25A20 protein. Other variant(s) that disrupt this region (p.Ala281Val) have been observed in individuals with SLC25A20-related conditions (PMID: 15365988). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000792302	SCV001361222	pathogenic	Carnitine acylcarnitine translocase deficiency	2019-02-11	criteria provided, single submitter	clinical testing	Variant summary: The variant, SLC25A20 c.804delG (p.Phe269SerfsX4) 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 7.2e-06 in 277230 control chromosomes (gnomAD) and has been reported in the literature in individuals affected with Carnitine-Acylcarnitine Translocase Deficiency (Costa _2003, Wang _2011). These data indicate that the variant may 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 (Costa _2003). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.