ClinVar Miner

Submissions for variant NM_001173990.3(TMEM216):c.218G>A (p.Arg73His)

dbSNP: rs201108965
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001038780 SCV001202273 pathogenic Familial aplasia of the vermis 2024-02-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 73 of the TMEM216 protein (p.Arg73His). This variant is present in population databases (rs201108965, gnomAD 0.01%). This missense change has been observed in individual(s) with Joubert syndrome-related disorders (PMID: 20512146). ClinVar contains an entry for this variant (Variation ID: 198). 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.
Baylor Genetics RCV000000221 SCV004206193 likely pathogenic Joubert syndrome 2 2024-02-07 criteria provided, single submitter clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV000024013 SCV005373839 likely pathogenic Meckel syndrome, type 2 2024-09-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005049302 SCV005683844 likely pathogenic Joubert syndrome 2; Meckel syndrome, type 2 2024-03-01 criteria provided, single submitter clinical testing
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV000000221 SCV005686447 likely pathogenic Joubert syndrome 2 criteria provided, single submitter research A known missense variant, c.218G>A (Valente EM et al., 2010, ClinVar ID: VCV000000198.14) in exon 3 of TMEM216 gene was observed in homozygous state in the proband. On segregation, the variant was observed in heterozygous state in the parents. The variant c.218G>A has been observed in heterozygous state in seven individuals in gnomAD (v4.1) population database (allele frequency: 0.000004338). This variant is absent in our in-house data of 3492 exomes.
OMIM RCV000000221 SCV000020364 pathogenic Joubert syndrome 2 2010-07-01 no assertion criteria provided literature only
OMIM RCV000024013 SCV000045304 pathogenic Meckel syndrome, type 2 2010-07-01 no assertion criteria provided literature only

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