ClinVar Miner

Submissions for variant NM_030773.4(TUBB1):c.952C>T (p.Arg318Trp)

gnomAD frequency: 0.00003  dbSNP: rs121918555
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851914 SCV000899995 likely pathogenic Macrothrombocytopenia 2019-02-01 criteria provided, single submitter research
Invitae RCV002512603 SCV003443381 pathogenic not provided 2022-05-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 318 of the TUBB1 protein (p.Arg318Trp). This variant is present in population databases (rs121918555, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of TUBB1-related macrothrombocytopenia (PMID: 18849486, 31064749, 33400601). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 425). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). Experimental studies have shown that this missense change affects TUBB1 function (PMID: 18849486). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000000453 SCV003816022 likely pathogenic Macrothrombocytopenia, isolated, 1, autosomal dominant 2022-02-09 criteria provided, single submitter clinical testing
OMIM RCV000000453 SCV000020602 pathogenic Macrothrombocytopenia, isolated, 1, autosomal dominant 2009-01-08 no assertion criteria provided literature only
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas RCV000000453 SCV004041702 likely pathogenic Macrothrombocytopenia, isolated, 1, autosomal dominant 2023-10-09 no assertion criteria provided clinical testing

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