Submissions for variant NM_003850.3(SUCLA2):c.236C>T (p.Ser79Leu)

gnomAD frequency: 0.00062  dbSNP: rs142289138

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000186185	SCV000239211	uncertain significance	not provided	2022-03-16	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Claritas Genomics	RCV000449628	SCV000537850	uncertain significance	Global developmental delay	2017-02-21	criteria provided, single submitter	clinical testing
Invitae	RCV001089257	SCV000768574	likely benign	Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	2024-01-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001089257	SCV001267086	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.
Ambry Genetics	RCV003278685	SCV003973310	likely benign	Inborn genetic diseases	2023-05-01	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003927728	SCV004737765	likely benign	SUCLA2-related disorder	2023-03-07	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).