Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001332477 | SCV001524812 | uncertain significance | Mitochondrial complex 1 deficiency, nuclear type 6 | 2019-08-15 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003994270 | SCV004814032 | uncertain significance | not specified | 2024-02-20 | criteria provided, single submitter | clinical testing | Variant summary: NDUFS2 c.422A>G (p.Tyr141Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251448 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.422A>G has been reported in the literature in heterozygous individuals without a reported second variant affected with Mitochondrial Complex I Deficiency or Leigh syndrome (e.g. Jou_2019, Tuppen_2010). These reports do not provide unequivocal conclusions about association of the variant with Mitochondrial Complex I Deficiency, Nuclear Type 6. One publication reports experimental evidence evaluating an impact on protein function showing severely decreased levels of dNADH oxidase activity in an E.coli system, however, does not allow convincing conclusions about the variant effect (e.g. Alkhaldi_2023). The following publications have been ascertained in the context of this evaluation (PMID: 36462614, 30634555, 20819849). ClinVar contains an entry for this variant (Variation ID: 1030813). Based on the evidence outlined above, the variant was classified as uncertain significance. |