Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000195688 | SCV000251882 | uncertain significance | not provided | 2013-09-30 | criteria provided, single submitter | clinical testing | p.Tyr53Cys (TAC>TGC): c.158 A>G in exon 3 of the NDUFS2 gene (NM_004550.4). The Y53C variant of unknown significance in the NDUFS2 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is semi-conservative as both Tyrosine and Cysteine are uncharged, polar amino acids, but the introduction of a Cysteine residue may affect disulfide bonds in the NDUFS2 protein. The change occurs at a highly conserved position in the NDUFS2 protein; however, in-silico analyses are not consistent in their predictions of whether or not Y53C is damaging to the NDUFS2 protein. Therefore, based on the currently available information, it is unclear whether Y53C is a disease-causing mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s). |
| Baylor Genetics | RCV001332476 | SCV001524811 | uncertain significance | Mitochondrial complex I deficiency, nuclear type 1 | 2019-02-14 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Genome- |
RCV003343695 | SCV004048798 | uncertain significance | Mitochondrial complex 1 deficiency, nuclear type 6 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003387798 | SCV004100026 | uncertain significance | not specified | 2023-09-20 | criteria provided, single submitter | clinical testing | Variant summary: NDUFS2 c.158A>G (p.Tyr53Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251370 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.158A>G has been reported in the literature in compound heterozygous individuals affected with non-syndromic Leber hereditary optic neuropathy (LHON)-like optic neuropathy. (e.g., Gerber_2017), and the variant was shown to segregate with disease among three siblings. These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (e.g., Gerber_2017). The following publication was ascertained in the context of this evaluation (PMID: 28031252). One submitter has reported clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| OMIM | RCV003389320 | SCV004101400 | pathogenic | Leber-like hereditary optic neuropathy, autosomal recessive 2 | 2024-01-09 | no assertion criteria provided | literature only |