Submissions for variant NM_001173990.3(TMEM216):c.217C>T (p.Arg73Cys)

gnomAD frequency: 0.00001  dbSNP: rs779526456

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
UW Hindbrain Malformation Research Program, University of Washington	RCV000201742	SCV000256485	pathogenic	Joubert syndrome 2	2015-02-23	criteria provided, single submitter	research
Eurofins Ntd Llc (ga)	RCV000595708	SCV000704860	uncertain significance	not provided	2016-12-27	criteria provided, single submitter	clinical testing
Invitae	RCV001053459	SCV001217720	pathogenic	Familial aplasia of the vermis	2024-01-05	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 73 of the TMEM216 protein (p.Arg73Cys). This variant is present in population databases (rs779526456, gnomAD 0.003%). This missense change has been observed in individual(s) with Joubert syndrome or Meckel syndrome (PMID: 20512146, 26092869). ClinVar contains an entry for this variant (Variation ID: 217705). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects TMEM216 function (PMID: 20512146). This variant disrupts the p.Arg73 amino acid residue in TMEM216. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20036350, 20512146, 26092869, 26673778). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814113	SCV001755636	likely pathogenic	Abnormality of the nervous system	2021-07-10	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000595708	SCV002016900	likely pathogenic	not provided	2021-01-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000201742	SCV004206195	likely pathogenic	Joubert syndrome 2	2023-10-17	criteria provided, single submitter	clinical testing