Submissions for variant NM_016464.5(TMEM138):c.307del (p.Arg103fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002913653	SCV003254426	pathogenic	Joubert syndrome 16	2022-04-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg103Alafs*23) in the TMEM138 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 60 amino acid(s) of the TMEM138 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Joubert syndrome and related disorders (PMID: 26489029, 32404165). This variant disrupts a region of the TMEM138 protein in which other variant(s) (p.Ala126Thr) have been determined to be pathogenic (PMID: 22282472). 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.
CeGaT Center for Human Genetics Tuebingen	RCV003222448	SCV003916720	likely pathogenic	not provided	2023-01-01	criteria provided, single submitter	clinical testing	TMEM138: PP4:Strong, PM2, PM3