Submissions for variant NM_003850.3(SUCLA2):c.68C>G (p.Thr23Arg)

dbSNP: rs538760468

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000701548	SCV000384523	uncertain significance	Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000701548	SCV000830352	uncertain significance	Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	2022-08-23	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 23 of the SUCLA2 protein (p.Thr23Arg). This variant is present in population databases (rs538760468, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SUCLA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 312272). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Athena Diagnostics	RCV002472985	SCV002770760	uncertain significance	not provided	2021-08-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002520887	SCV003533044	uncertain significance	Inborn genetic diseases	2022-10-03	criteria provided, single submitter	clinical testing	The c.68C>G (p.T23R) alteration is located in exon 1 (coding exon 1) of the SUCLA2 gene. This alteration results from a C to G substitution at nucleotide position 68, causing the threonine (T) at amino acid position 23 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.