Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002532030 | SCV003718917 | likely pathogenic | Inborn genetic diseases | 2022-01-20 | criteria provided, single submitter | clinical testing | The c.387delT (p.M130Cfs*35) alteration, located in exon 3 (coding exon 3) of the NDUFA6 gene, consists of a deletion of one nucleotide at position 387, causing a translational frameshift with a predicted alternate stop codon after 35 amino acids. This alteration occurs at the 3' terminus of the NDUFA6 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 15% of the protein. Premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). Based on data from gnomAD, the c.387delT allele has an overall frequency of 0.01% (16/282896) total alleles studied. The highest observed frequency was 0.01% (16/129192) of European (non-Finnish) alleles. This variant, designated as 309del was confirmed in trans with a second NDUFA6 frameshift variant in an infant presenting with unusual movements suggestive of seizure disorder, elevated blood gas lactate, abnormal brain MRI with white matter changes, and deterioration as a result of status epilepticus, apnea episodes, and persistent lactic acidosis (Alston, 2018). Based on the available evidence, this alteration is classified as likely pathogenic. |
| Wellcome Centre for Mitochondrial Research, |
RCV000680373 | SCV000787626 | pathogenic | Mitochondrial disease | 2018-07-19 | no assertion criteria provided | clinical testing | |
| OMIM | RCV000710001 | SCV000840366 | pathogenic | Mitochondrial complex 1 deficiency, nuclear type 33 | 2018-12-13 | no assertion criteria provided | literature only |