Submissions for variant NM_003849.4(SUCLG1):c.236G>A (p.Gly79Asp)

gnomAD frequency: 0.00099  dbSNP: rs143030960

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000239306	SCV000297146	uncertain significance	not specified	2015-10-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000369613	SCV000432150	uncertain significance	Mitochondrial DNA depletion syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000390394	SCV000432151	uncertain significance	Mitochondrial DNA depletion syndrome 9	2018-01-12	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000428598	SCV000511721	uncertain significance	not provided	2016-12-01	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000428598	SCV000884622	uncertain significance	not provided	2017-07-07	criteria provided, single submitter	clinical testing	The p.Gly79Asp variant (rs143030960) has not been reported in the medical literature; although, it is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 203970). It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in Ashkenazi Jewish populations of 0.67% (identified in 68 out of 10,150 chromosomes). The glycine at codon 79 is highly conserved considering 11 species up to Baker’s yeast (Alamut software v2.9), and computational analyses suggest this variant has a significant effect on SUCLG1 protein structure/function (SIFT: damaging, PolyPhen2: probably damaging, and Mutation Taster: disease causing). However, based on the available information, the clinical significance of the p.Gly79Asp variant cannot be determined with certainty.
Fulgent Genetics, Fulgent Genetics	RCV000390394	SCV000895507	uncertain significance	Mitochondrial DNA depletion syndrome 9	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000390394	SCV001015698	likely benign	Mitochondrial DNA depletion syndrome 9	2024-01-22	criteria provided, single submitter	clinical testing
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	RCV000390394	SCV002574825	uncertain significance	Mitochondrial DNA depletion syndrome 9	2022-09-22	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000390394	SCV003818141	uncertain significance	Mitochondrial DNA depletion syndrome 9	2023-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000428598	SCV004155100	uncertain significance	not provided	2023-07-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003955118	SCV004767886	likely benign	SUCLG1-related condition	2020-03-23	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).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000428598	SCV001744023	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000428598	SCV001976164	uncertain significance	not provided		no assertion criteria provided	clinical testing