Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000331047 | SCV000335491 | likely pathogenic | not provided | 2015-09-21 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000778864 | SCV000915261 | uncertain significance | Mitochondrial complex V (ATP synthase) deficiency nuclear type 2 | 2017-09-01 | criteria provided, single submitter | clinical testing | The TMEM70 c.720_723delAGAA (p.Glu241AsnfsTer24) variant results in a frameshift and is predicted to cause an elongation of the protein. It 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 frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for mitochondrial complex V (ATP synthase) deficiency. |
| Invitae | RCV000778864 | SCV001420887 | uncertain significance | Mitochondrial complex V (ATP synthase) deficiency nuclear type 2 | 2022-09-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu241Asnfs*24) in the TMEM70 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 20 amino acid(s) of the TMEM70 protein. This variant is present in population databases (rs746973761, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TMEM70-related conditions. ClinVar contains an entry for this variant (Variation ID: 283424). 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. |