ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.50T>A (p.Leu17Ter)

dbSNP: rs1563672487
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000732837 SCV000860829 likely pathogenic not provided 2018-05-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003768227 SCV004578918 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2023-05-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 596873). This premature translational stop signal has been observed in individual(s) with clinical features of TMEM67-related conditions (PMID: 32404165). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu17*) in the TMEM67 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TMEM67 are known to be pathogenic (PMID: 20232449, 23559409).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004586909 SCV005077695 pathogenic Joubert syndrome and related disorders 2024-04-17 criteria provided, single submitter clinical testing Variant summary: TMEM67 c.50T>A (p.Leu17X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251482 control chromosomes. c.50T>A has been reported in the literature in at-least one individual affected with Joubert Syndrome And Related Disorders (example: Issa_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 32404165). ClinVar contains an entry for this variant (Variation ID: 596873). Based on the evidence outlined above, the variant was classified as pathogenic.

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