Submissions for variant NM_152906.7(TANGO2):c.634C>T (p.Gln212Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003671895	SCV004385366	pathogenic	not provided	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln212*) in the TANGO2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TANGO2 are known to be pathogenic (PMID: 26805781, 26805782). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TANGO2-related conditions. For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV004764859	SCV005374831	likely pathogenic	Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome		criteria provided, single submitter	clinical testing	The observed stop gained c.634C>T (p.Gln212Ter) variant in TANGO2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gln212Ter variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Computational evidence (MutationTaster - Disease causing) predicts damaging effect on protein structure and function for this variant. The reference amino acid of p.Gln212Ter in TANGO2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal (p.Gln212Ter) in the TANGO2 gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in TANGO2 gene have been previously reported to be disease causing (Kremer et al., 2016). However, additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic.