Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostics Services |
RCV003236686 | SCV003935157 | likely pathogenic | Mitochondrial complex 1 deficiency, nuclear type 5 | 2023-06-22 | criteria provided, single submitter | clinical testing | The c.2102G>A variant is not present in publicly available population databases like 1000 Genomes, EVS, Indian Exome Database or in our in-house exome database. The variant is present in gnomAD and ExAC at low frequencies. This variant has been previously observed in affected individuals, published in literature [PMIDs: 25615419, 34716721, 35012964] and reported to the Human Gene Mutation Database (HGMD ID: CM1516823). In silico pathogenicity prediction programs like SIFT, PolyPhen2, MutationTaster2, CADD etc predicted this variant to be likely deleterious, however these predictions were not confirmed by published functional studies. |
| Labcorp Genetics |
RCV003561257 | SCV004293056 | uncertain significance | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 701 of the NDUFS1 protein (p.Ser701Asn). This variant is present in population databases (rs750056825, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of complex I deficiency and/or Leigh syndrome (PMID: 25615419, 34716721). ClinVar contains an entry for this variant (Variation ID: 2506502). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. |