Submissions for variant NM_017866.6(TMEM70):c.578_579del (p.Thr193fs)

dbSNP: rs777501387

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484311	SCV000566851	pathogenic	not provided	2024-04-28	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in abnormal protein length as the last 68 amino acids are replaced with 5 different amino acids, and other similar variants have been reported in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25326274, 21147908, 24740313)
Invitae	RCV001050497	SCV001214607	likely pathogenic	Mitochondrial complex V (ATP synthase) deficiency nuclear type 2	2022-11-10	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts a region of the TMEM70 protein in which other variant(s) (p.His234Pro) have been observed in individuals with TMEM70-related conditions (PMID: 24740313). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 419199). This premature translational stop signal has been observed in individual(s) with ATP synthase deficiency (PMID: 21147908). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs777501387, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Thr193Serfs*6) in the TMEM70 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 68 amino acid(s) of the TMEM70 protein.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001050497	SCV004805469	likely pathogenic	Mitochondrial complex V (ATP synthase) deficiency nuclear type 2	2024-03-25	criteria provided, single submitter	research
OMIM	RCV001050497	SCV000045240	pathogenic	Mitochondrial complex V (ATP synthase) deficiency nuclear type 2	2011-03-01	no assertion criteria provided	literature only