Submissions for variant NM_001379200.1(TBX1):c.1159G>A (p.Gly387Ser)

gnomAD frequency: 0.00107  dbSNP: rs565927787

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000621315	SCV000736355	likely benign	Cardiovascular phenotype	2021-05-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000877083	SCV001019756	likely benign	DiGeorge syndrome	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001584433	SCV001813156	likely benign	not provided	2020-07-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20453311)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004586830	SCV005077627	likely benign	not specified	2024-04-29	criteria provided, single submitter	clinical testing	Variant summary: TBX1 c.1132G>A (p.Gly378Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00023 in 1309378 control chromosomes, predominantly at a frequency of 0.0042 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database strongly suggests that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1132G>A has been reported in the literature in an individuals affected with midline facial defects with hypertelorism without strong evidence of causality (Simioni_2010). This report does not provide unequivocal conclusions about association of the variant with TBX1-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 20453311). ClinVar contains an entry for this variant (Variation ID: 518829). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003917978	SCV004731823	likely benign	TBX1-related disorder	2020-04-28	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).