Submissions for variant NM_000387.6(SLC25A20):c.779_781del (p.Glu260del)

dbSNP: rs754871147

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000385873	SCV000445209	uncertain significance	Carnitine acylcarnitine translocase deficiency	2017-04-28	criteria provided, single submitter	clinical testing	The SLC25A20 c.779_781delAAG (p.Glu260del) variant has been identified in a compound heterozygous state with a missense variant in one individual with elevated long chain fatty acids and an acylcarnitine profile consistent with carnitine-acylcarnitine translocase deficiency (Wang et al. 2011). Control data are unavailable for this variant, which is reported at a frequency of 0.001814 in the European (Finnish) population of the Exome Aggregation Consortium. In silico modelling experiments showed that the Glu260 amino acid residue is conserved and critical for maintaining the enzyme cavity and substrate recognition. The evidence for this variant is limited. The p.Glu260del variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for carnitine-acylcarnitine translocase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000385873	SCV001386068	uncertain significance	Carnitine acylcarnitine translocase deficiency	2025-01-20	criteria provided, single submitter	clinical testing	This variant, c.779_781del, results in the deletion of 1 amino acid(s) of the SLC25A20 protein (p.Glu260del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs754871147, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with carnitine-acylcarnitine translocase deficiency (PMID: 21605995). ClinVar contains an entry for this variant (Variation ID: 345940). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001753811	SCV001986132	uncertain significance	not provided	2021-01-29	criteria provided, single submitter	clinical testing	In-frame deletion of 1 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21605995, 32340404)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002271492	SCV002556231	likely benign	not specified	2022-06-29	criteria provided, single submitter	clinical testing	Variant summary: SLC25A20 c.779_781delAAG (p.Glu260del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 0.00029 in 282850 control chromosomes, predominantly at a frequency of 0.0018 within the Finnish subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Finnish control individuals in the gnomAD database is approximately two fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC25A20 causing Carnitine-Acylcarnitine Translocase Deficiency phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Finnish origin. c.779_781delAAG has been reported in the literature in at least one individual affected with Carnitine-Acylcarnitine Translocase Deficiency (Wang_2011). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.