Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000618252 | SCV000736024 | uncertain significance | Cardiovascular phenotype | 2018-08-29 | criteria provided, single submitter | clinical testing | The p.G350D variant (also known as c.1049G>A), located in coding exon 8 of the TBX1 gene, results from a G to A substitution at nucleotide position 1049. The glycine at codon 350 is replaced by aspartic acid, an amino acid with similar properties. This alteration has been reported in an individual with an aortic arch anomaly; however, clinical details were limited (Gong W et al. J. Med. Genet. 2001 Dec;38:E45). This amino acid position is not well conserved on limited sequence alignment. 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. |
Fulgent Genetics, |
RCV000765609 | SCV000896933 | uncertain significance | Conotruncal heart malformations; Velocardiofacial syndrome; DiGeorge syndrome; Tetralogy of Fallot | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000876712 | SCV001019319 | likely benign | DiGeorge syndrome | 2024-01-25 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001574708 | SCV001801574 | likely benign | not provided | 2024-06-15 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
Ce |
RCV001574708 | SCV001962426 | uncertain significance | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479173 | SCV004223275 | likely benign | not specified | 2023-11-30 | criteria provided, single submitter | clinical testing | Variant summary: TBX1 c.1049G>A (p.Gly350Asp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00082 (1096 variant alleles) in 1345326 control chromosomes in the gnomAD v4 database. c.1049G>A has been reported in the literature in individuals affected with aortic arch anomalies or congenital heart defects (Gong_2001, Zodanu_2021). These reports do not provide unequivocal conclusions about association of the variant with TBX1-Related Disorders. Although reported in the literature in individuals affected with aortic arch anomalies or congenital heart defects (Gong_2001, Zodanu_2021), to our knowledge no penetrant association of this variant with TBX1-related disorders and no experimental evidence has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29500247, 11748311, 29250159, 33995479). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=3) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as likely benign. |