ClinVar Miner

Submissions for variant NM_000660.7(TGFB1):c.466C>T (p.Arg156Cys)

gnomAD frequency: 0.00003  dbSNP: rs200482214
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002010359 SCV002279302 pathogenic not provided 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 156 of the TGFB1 protein (p.Arg156Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant TGFB1-related conditions (PMID: 11260231, 15894597, 23453470, 23824952, 31899347). ClinVar contains an entry for this variant (Variation ID: 1498982). 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 TGFB1 protein function. Experimental studies have shown that this missense change affects TGFB1 function (PMID: 19584867). For these reasons, this variant has been classified as Pathogenic.
AiLife Diagnostics, AiLife Diagnostics RCV002010359 SCV002501265 likely pathogenic not provided 2021-06-18 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003426281 SCV004118469 pathogenic TGFB1-related condition 2023-06-06 criteria provided, single submitter clinical testing The TGFB1 c.466C>T variant is predicted to result in the amino acid substitution p.Arg156Cys. This variant has been reported in multiple unrelated individuals with Camurati-Engelmann disease (Hecht et al. 2001. PubMed ID: 11260231; Janssens et al. 2005. PubMed ID: 15894597; Collet et al. 2013. PubMed ID: 23824952; Savoie et al. 2013. PubMed ID: 23453470). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In ClinVar, this variant has been interpreted as pathogenic/likely pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/1498982/). This variant is interpreted as pathogenic.

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