Submissions for variant NM_017866.6(TMEM70):c.359del (p.Thr120fs)

dbSNP: rs2131236556

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002031623	SCV002312453	pathogenic	Mitochondrial complex V (ATP synthase) deficiency nuclear type 2	2022-10-29	criteria provided, single submitter	clinical testing	This variant disrupts a region of the TMEM70 protein in which other variant(s) (p.Tyr166Cysfs*7) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1524311). This sequence change creates a premature translational stop signal (p.Thr120Asnfs*34) in the TMEM70 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 141 amino acid(s) of the TMEM70 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with TMEM70 deficiency (PMID: 25326274).
Intergen, Intergen Genetics and Rare Diseases Diagnosis Center	RCV002031623	SCV004015110	pathogenic	Mitochondrial complex V (ATP synthase) deficiency nuclear type 2	2023-07-21	criteria provided, single submitter	clinical testing
GeneDx	RCV004719228	SCV005325351	likely pathogenic	not provided	2023-12-19	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in abnormal protein length as the last 141 amino acids are replaced with 33 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)