Submissions for variant NM_002496.4(NDUFS8):c.229C>T (p.Arg77Trp)

gnomAD frequency: 0.00002  dbSNP: rs146766138

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523226	SCV000617290	uncertain significance	not provided	2017-07-25	criteria provided, single submitter	clinical testing	The R77W variant in the NDUFS8 gene has previously been reported in an individual with isolated complex I deficiency, who also harbors a second variant in this gene. Complex I activity was significantly decreased in both the muscle and fibroblasts of this individual (Haack et al., 2012). This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R77W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on currently available evidence, we interpret R77W as a variant of uncertain significance.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000033054	SCV004805316	uncertain significance	Mitochondrial complex 1 deficiency, nuclear type 2	2024-03-25	criteria provided, single submitter	research
OMIM	RCV000033054	SCV000056834	pathogenic	Mitochondrial complex 1 deficiency, nuclear type 2	2012-04-01	no assertion criteria provided	literature only