Submissions for variant NM_024120.5(NDUFAF5):c.821T>A (p.Leu274Gln)

dbSNP: rs1040187200

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV000985087	SCV001520719	uncertain significance	Mitochondrial complex 1 deficiency, nuclear type 16	2019-09-24	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV001555266	SCV001776651	uncertain significance	not provided	2019-08-27	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31130284, 28454995)
Fulgent Genetics, Fulgent Genetics	RCV000985087	SCV002778535	uncertain significance	Mitochondrial complex 1 deficiency, nuclear type 16	2022-05-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003117659	SCV003801180	uncertain significance	not specified	2023-01-24	criteria provided, single submitter	clinical testing	Variant summary: NDUFAF5 c.821T>A (p.Leu274Gln) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251344 control chromosomes. c.821T>A has been reported in the literature as a homozygous genotype in at-least one individual affected with features of Mitochondrial complex 1 deficiency/Leigh Syndrome, however, the possibility of additional independent homozygous cases or cohort overlap with the primary report in subsequent citations cannot be ruled out (example, PMID: 28454995, 31130284, 34645488). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000985087	SCV005016570	uncertain significance	Mitochondrial complex 1 deficiency, nuclear type 16	2024-03-14	criteria provided, single submitter	clinical testing
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000985087	SCV001133047	likely pathogenic	Mitochondrial complex 1 deficiency, nuclear type 16	2019-09-26	no assertion criteria provided	clinical testing