Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002470524 | SCV002768664 | uncertain significance | Mitochondrial complex 1 deficiency, nuclear type 5 | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_005006.6(NDUFS1):c.134C>A in exon 3 of 19 of the NDUFS1 gene (NB: This variant is non-coding in alternative transcripts). This substitution is predicted to create a moderate amino acid change from proline to glutamine at position 45 of the protein, NP_004997.4(NDUFS1):p.(Pro45Gln). The proline at this position has very high conservation (100 vertebrates, UCSC), and is located within the 2Fe-2S iron-sulfur cluster binding domain. In silico software predictions of the pathogenicity of this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is not present in the gnomAD population database, and has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS). |