ClinVar Miner

Submissions for variant NM_020461.4(TUBGCP6):c.3689C>G (p.Ser1230Trp)

dbSNP: rs201398979
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001913330 SCV002169544 uncertain significance not provided 2022-06-23 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 1230 of the TUBGCP6 protein (p.Ser1230Trp). This variant is present in population databases (rs201398979, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with TUBGCP6-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The tryptophan amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV004771512 SCV005382298 uncertain significance Microcephaly and chorioretinopathy 1 2023-05-20 criteria provided, single submitter clinical testing The missense variant c.3689C>G (p.Ser1230Trp) in the TUBGCP6 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.009%) in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Serine at position 1230 is changed to a Tryptophan changing protein sequence and it might alter its composition and physico- chemical properties. Multiple lines of computational evidence (Polyphen, SIFT and MutationTaster) predict no damaging effect on protein structure and function for this variant. The amino acid change p.Ser1230Trp in TUBGCP6 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

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