ClinVar Miner

Submissions for variant NM_001128148.3(TFRC):c.2186C>T (p.Thr729Met)

gnomAD frequency: 0.00013  dbSNP: rs202242239
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001333105 SCV001525595 uncertain significance TFRC-related combined immunodeficiency 2018-11-26 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001865776 SCV002123904 uncertain significance not provided 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 729 of the TFRC protein (p.Thr729Met). This variant is present in population databases (rs202242239, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TFRC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1031313). 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 not expected to disrupt TFRC protein function with a negative predictive value of 80%. 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.

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