Submissions for variant NM_002495.4(NDUFS4):c.198A>C (p.Gly66=)

gnomAD frequency: 0.96579  dbSNP: rs31304

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000280222	SCV000457888	benign	Mitochondrial complex I deficiency, nuclear type 1	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000342200	SCV000457889	benign	Leigh syndrome	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000117714	SCV000917865	benign	not specified	2018-09-17	criteria provided, single submitter	clinical testing	Variant summary: NDUFS4 c.198A>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.96 in 275374 control chromosomes, suggesting that it is the major allele (the variant most commonly observed in the general population), therefore is benign. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Mendelics	RCV000342200	SCV001136837	benign	Leigh syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Invitae	RCV000676474	SCV001731657	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000676474	SCV001834824	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000280222	SCV002016113	benign	Mitochondrial complex I deficiency, nuclear type 1	2021-09-05	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000117714	SCV000151961	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Mayo Clinic Laboratories, Mayo Clinic	RCV000676474	SCV000802256	benign	not provided	2016-02-19	no assertion criteria provided	clinical testing