ClinVar

Description

A heterozygous missense variant was identified, NM_005002.4(NDUFA9):c.224G>T in exon 3 of 11 of the NDUFA9 gene. This substitution is predicted to create a major amino acid change from arginine to leucine at position 75 of the protein, NP_004993.1(NDUFA9):p.(Arg75Leu). The arginine at this position has moderate conservation (100 vertebrates, UCSC), and is located within the epimerase functional domain. In silico software predicts this variant to be disease causing (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.075% (207 heterozygotes, 2 homozygotes). An alternative residue change at the same location has been reported in the gnomAD database at a frequency of 0.086%. The variant has been previously reported as both a VUS and as likely pathogenic (ClinVar). A different variant in the same codon resulting in a changes to cysteine has been described as a VUS (LOVD). Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS).