Submissions for variant NM_001379200.1(TBX1):c.1352G>C (p.Arg451Pro)

gnomAD frequency: 0.00006  dbSNP: rs755937050

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000620652	SCV000735639	uncertain significance	Cardiovascular phenotype	2017-07-12	criteria provided, single submitter	clinical testing	The p.R442P variant (also known as c.1325G>C), located in coding exon 8 of the TBX1 gene, results from a G to C substitution at nucleotide position 1325. The arginine at codon 442 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000876591	SCV001019182	likely benign	DiGeorge syndrome	2023-11-25	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001821753	SCV002064755	uncertain significance	not specified	2020-09-10	criteria provided, single submitter	clinical testing	DNA sequence analysis of the TBX1 gene demonstrated a sequence change, c.1325G>C, in exon 9 that results in an amino acid change, p.Arg442Pro. This sequence change does not appear to have been previously described in patients with TBX1-related disorders. This sequence change has been described in the gnomAD database with a low population frequency of 0.045% (dbSNP rs755937050). The p.Arg442Pro change affects a moderately conserved amino acid residue of the TBX1 protein. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg442Pro substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Arg442Pro change remains unknown at this time.
CeGaT Center for Human Genetics Tuebingen	RCV003437330	SCV004152119	benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	TBX1: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003892392	SCV004714730	likely benign	TBX1-related disorder	2021-10-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).