ClinVar Miner

Submissions for variant NM_024809.5(TCTN2):c.1967G>C (p.Trp656Ser)

gnomAD frequency: 0.00002  dbSNP: rs200159224
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001771531 SCV002002809 uncertain significance not provided 2022-05-24 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002540550 SCV003299284 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2023-06-15 criteria provided, single submitter clinical testing This variant is present in population databases (rs200159224, gnomAD 0.007%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TCTN2 protein function. ClinVar contains an entry for this variant (Variation ID: 1314300). This variant has not been reported in the literature in individuals affected with TCTN2-related conditions. This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 656 of the TCTN2 protein (p.Trp656Ser).
Ambry Genetics RCV003355537 SCV004063905 uncertain significance Inborn genetic diseases 2023-07-05 criteria provided, single submitter clinical testing The c.1967G>C (p.W656S) alteration is located in exon 17 (coding exon 17) of the TCTN2 gene. This alteration results from a G to C substitution at nucleotide position 1967, causing the tryptophan (W) at amino acid position 656 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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