Submissions for variant NM_005996.4(TBX3):c.613C>T (p.His205Tyr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002735638	SCV003011354	uncertain significance	Ulnar-mammary syndrome	2023-08-02	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 205 of the TBX3 protein (p.His205Tyr). This variant is present in population databases (rs749487839, gnomAD 0.04%), 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 TBX3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1970912). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
PreventionGenetics, part of Exact Sciences	RCV003984274	SCV004799963	uncertain significance	TBX3-related disorder	2024-02-26	no assertion criteria provided	clinical testing	The TBX3 c.613C>T variant is predicted to result in the amino acid substitution p.His205Tyr. This variant was found in a mother and child with obesity, along with some other features of TBX3-related ulnar-mammary-syndrome (Xu et al. 2020. PubMed Central ID: PMC7209158). This variant is reported in 0.045% of alleles in individuals of Latino descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.