ClinVar Miner

Submissions for variant NM_015631.6(TCTN3):c.3G>A (p.Met1Ile)

gnomAD frequency: 0.00002  dbSNP: rs745688122
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program, University of Washington RCV000201547 SCV000256480 pathogenic Joubert syndrome 18 2015-02-23 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000796275 SCV000935781 pathogenic Orofacial-digital syndrome IV; Joubert syndrome 18 2024-10-02 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the TCTN3 mRNA. The next in-frame methionine is located at codon 152. This variant is present in population databases (rs745688122, gnomAD 0.02%). Disruption of the initiator codon has been observed in individual(s) with personal or family history of Joubert syndrome (PMID: 26092869; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 217703). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003227713 SCV003924545 likely pathogenic not provided 2022-11-10 criteria provided, single submitter clinical testing Also reported with a variant on the opposite allele (in trans) in a patient with features of a TCTN3-related disorder in the published literature (Huljev Frkovic et al., 2022); Initiation codon variant in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26092869, 35170189)
Eurofins-Biomnis RCV000201547 SCV003935115 likely pathogenic Joubert syndrome 18 2022-12-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782310 SCV005395372 pathogenic Joubert syndrome and related disorders 2024-09-19 criteria provided, single submitter clinical testing Variant summary: TCTN3 c.3G>A (p.Met1Ile) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. The variant allele was found at a frequency of 3.2e-05 in 155526 control chromosomes. c.3G>A has been reported in the literature in individuals affected with Joubert Syndrome And Related Disorders. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26092869, 35170189, 37217489). ClinVar contains an entry for this variant (Variation ID: 217703). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000796275 SCV005678478 likely pathogenic Orofacial-digital syndrome IV; Joubert syndrome 18 2024-01-23 criteria provided, single submitter clinical testing

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