ClinVar Miner

Submissions for variant NM_015631.6(TCTN3):c.1520dup (p.Gly508fs)

gnomAD frequency: 0.00004  dbSNP: rs755903123
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001974853 SCV002208417 pathogenic Orofacial-digital syndrome IV; Joubert syndrome 18 2024-08-20 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the TCTN3 gene (p.Gly508Argfs*106). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 100 amino acid(s) of the TCTN3 protein and extend the protein by 5 additional amino acid residues. This variant is present in population databases (rs755903123, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TCTN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1439041). This variant results in an extension of the TCTN3 protein. Other variant(s) that result in a similarly extended protein product (p.Asn512Valfs*103) have been determined to be pathogenic (Invitae). This suggests that these extensions are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226506 SCV003923094 uncertain significance not specified 2023-03-01 criteria provided, single submitter clinical testing Variant summary: TCTN3 c.1520dupT (p.Gly508ArgfsX106) causes a frameshift which disrupts the last 100 amino acids and results in an extension of the encoded protein. The variant allele was found at a frequency of 8e-06 in 251464 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1520dupT in individuals affected with Joubert Syndrome And Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic until further evidence becomes available.
Fulgent Genetics, Fulgent Genetics RCV001974853 SCV005678460 likely pathogenic Orofacial-digital syndrome IV; Joubert syndrome 18 2024-04-30 criteria provided, single submitter clinical testing

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