Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV002510712 | SCV002820244 | uncertain significance | Mitochondrial complex 1 deficiency, nuclear type 5 | criteria provided, single submitter | clinical testing | The missense variant p.L516F in NDUFS1 (NM_005006.7) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.L516F variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a small physicochemical difference between leucine and phenylalanine, which is not likely to impact secondary protein structure as these residues share similar properties. The p.L516F missense variant is predicted to be damaging by both SIFT and PolyPhen2. The leucine residue at codon 516 of NDUFS1 is conserved in all mammalian species. The nucleotide c.1546 in NDUFS1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |