Submissions for variant NM_001379200.1(TBX1):c.1304A>G (p.Tyr435Cys)

gnomAD frequency: 0.00001  dbSNP: rs1386894564

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001347685	SCV001541958	uncertain significance	DiGeorge syndrome	2025-01-23	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 426 of the TBX1 protein (p.Tyr426Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TBX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1043558). 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	RCV003399134	SCV004103505	uncertain significance	TBX1-related disorder	2023-03-10	criteria provided, single submitter	clinical testing	The TBX1 c.1277A>G variant is predicted to result in the amino acid substitution p.Tyr426Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-19754179-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.