ClinVar Miner

Submissions for variant NM_004553.6(NDUFS6):c.247C>T (p.Arg83Trp)

gnomAD frequency: 0.00003  dbSNP: rs863224110
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199698 SCV000251904 likely pathogenic not provided 2014-06-03 criteria provided, single submitter clinical testing p.Arg83Trp (CGG>TGG): c.247 C>T in exon 3 of the NDUFS6 gene (NM_004553.3). The R83W variant that is likely pathogenic was identified in the NDUFS6 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R83W 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 highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001804934 SCV002051236 uncertain significance not specified 2021-12-18 criteria provided, single submitter clinical testing Variant summary: NDUFS6 c.247C>T (p.Arg83Trp) results in a non-conservative amino acid change located in the Zinc finger, CHCC-type domain (IPR019401) of 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 2.4e-05 in 251496 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.247C>T in individuals affected with Leigh Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000199698 SCV003470874 uncertain significance not provided 2022-04-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 83 of the NDUFS6 protein (p.Arg83Trp). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NDUFS6-related conditions. ClinVar contains an entry for this variant (Variation ID: 214820). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity RCV003129801 SCV003813537 uncertain significance Mitochondrial complex 1 deficiency, nuclear type 9 2021-09-08 criteria provided, single submitter clinical testing

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