ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.1964_1965dup (p.Gly656fs)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002308704 SCV002600831 likely pathogenic Joubert syndrome and related disorders 2022-10-03 criteria provided, single submitter clinical testing Variant summary: TMEM67 c.1964_1965dupAG (p.Gly656ArgfsX11) 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. Truncations downstream of this position have been classified as pathogenic in ClinVar and is associated with Joubert Syndrome in HGMD. The variant was absent in 251418 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1964_1965dupAG in individuals affected with Joubert Syndrome And Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003099119 SCV003475578 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2023-02-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly656Argfs*11) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TMEM67-related conditions. ClinVar contains an entry for this variant (Variation ID: 1723428). For these reasons, this variant has been classified as Pathogenic.

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