ClinVar Miner

Submissions for variant NM_001069.3(TUBB2A):c.872A>C (p.Gln291Pro)

dbSNP: rs863224939
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UCLA Clinical Genomics Center, UCLA RCV000195901 SCV000255499 likely pathogenic Complex cortical dysplasia with other brain malformations 5 2014-01-28 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000195901 SCV002512281 likely pathogenic Complex cortical dysplasia with other brain malformations 5 2022-02-10 criteria provided, single submitter clinical testing ACMG classification criteria: PS4 supporting, PM2 moderate, PM6, PP3 supporting
GeneDx RCV002264917 SCV002546687 likely pathogenic not provided 2022-07-02 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28840640, 32203252, 31589614, 25326637)
Invitae RCV002264917 SCV003483365 uncertain significance not provided 2022-03-23 criteria provided, single submitter clinical testing 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) performed at Invitae indicates that this missense variant is expected to disrupt TUBB2A protein function. ClinVar contains an entry for this variant (Variation ID: 217024). This missense change has been observed in individual(s) with TUBB2A-related conditions (PMID: 25326637). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 291 of the TUBB2A protein (p.Gln291Pro).
PreventionGenetics, part of Exact Sciences RCV003897431 SCV004709827 uncertain significance TUBB2A-related disorder 2023-12-12 criteria provided, single submitter clinical testing The TUBB2A c.872A>C variant is predicted to result in the amino acid substitution p.Gln291Pro. This variant was reported to have occurred de novo in an individual with developmental delay, short stature, seizures, ureteropelvic junction obstruction, constipation, hydronephrosis, clinodactyly, growth hormone deficiency, and Russell Silver syndrome (Lee et al. 2014. PubMed ID: 25326637, eTable 2). This variant was also reported in a presumably unaffected gamete donor in a large carrier screening study (Capalbo A et al 2019. PubMed ID: 31589614, supplemental table S1). At PreventionGenetics, we detected this variant in an individual with a neurodevelopmental phenotype, but it was inherited from a presumably unaffected parent (internal data). This variant has not been reported in a large population database, indicating it is rare. Although we suspect this variant may be pathogenic, at this time the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.
Diagnostic Laboratory, Strasbourg University Hospital RCV002274940 SCV002562772 uncertain significance Seizure no assertion criteria provided clinical testing

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