Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779561 | SCV000916235 | uncertain significance | Mitochondrial complex V (ATP synthase) deficiency nuclear type 2 | 2017-04-28 | criteria provided, single submitter | clinical testing | The TMEM70 c.782G>C (p.Ter261SerextTer17) variant is a stop-lost variant, which was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of stop-lost variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for the nuclear type of mitochondrial complex V (ATP synthase) deficiency. |
| Invitae | RCV000779561 | SCV003460527 | uncertain significance | Mitochondrial complex V (ATP synthase) deficiency nuclear type 2 | 2022-03-03 | criteria provided, single submitter | clinical testing | This sequence change disrupts the translational stop signal of the TMEM70 mRNA. It is expected to extend the length of the TMEM70 protein by 17 additional amino acid residues. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This protein extension has been observed in individual(s) with clinical features of TMEM70-related conditions (PMID: 24740313). ClinVar contains an entry for this variant (Variation ID: 632525). 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. |