ClinVar Miner

Submissions for variant NM_004551.3(NDUFS3):c.374G>A (p.Arg125His) (rs138867882)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479127 SCV000565318 likely pathogenic not provided 2015-07-22 criteria provided, single submitter clinical testing The R125H variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The R125H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000853270 SCV000996102 likely pathogenic Mitochondrial complex I deficiency 2018-01-18 criteria provided, single submitter clinical testing This variant has previously been reported as likely pathogenic by a clinical laboratory in the ClinVar database (ClinVar Variation ID 418381). However, no functional studies are available to confirm that the variant alters protein function. There are eight reports of the allele in the public reference database, gnomAD, thus the variant is rare. The p.Arg125 residue is highly conserved among eukaryotes and in silico algorithms predict a damaging effect of a histidine substitution on protein function. Based on the combined evidence, the variant is classified as likely pathogenic.

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