Submissions for variant NM_000387.6(SLC25A20):c.897dup (p.Asn300fs)

dbSNP: rs587776759

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000012915	SCV001554546	pathogenic	Carnitine acylcarnitine translocase deficiency	2021-03-17	criteria provided, single submitter	clinical testing	Variant summary: SLC25A20 c.897dupC (p.Asn300GlnfsX24) causes a frameshift which results in an extension of the protein. The variant allele was found at a frequency of 4e-06 in 250746 control chromosomes. c.897dupC has been reported in the literature in at-least two homozygous individuals affected with Carnitine-Acylcarnitine Translocase Deficiency and subsequently cited by others (example, Huizing_1997, Wang_2011, Ijlst_2001, Costa_2003, Palmieri_2020). These data indicate that the variant is likely to be associated with disease. At least two publications report experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in non-detectable to 10% of normal carnitine acylcarnitine translocase (CACT) activity (example, Huizing_1997, IJlst_2001). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000012915	SCV002243100	pathogenic	Carnitine acylcarnitine translocase deficiency	2023-02-16	criteria provided, single submitter	clinical testing	This variant is present in population databases (no rsID available, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this frameshift affects SLC25A20 function (PMID: 11162577). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 12132). This variant is also known as 955-959insC. This frameshift has been observed in individual(s) with carnitine-acylcarnitine translocase deficiency (PMID: 9399886; Invitae). This sequence change results in a frameshift in the SLC25A20 gene (p.Asn300Glnfs*24). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2 amino acid(s) of the SLC25A20 protein and extend the protein by 21 additional amino acid residues.
OMIM	RCV000012915	SCV000033156	pathogenic	Carnitine acylcarnitine translocase deficiency	1997-12-01	no assertion criteria provided	literature only