ClinVar Miner

Submissions for variant NM_000192.3(TBX5):c.787G>A (p.Val263Met) (rs147405081)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000180104 SCV000232478 likely benign not specified 2018-05-21 criteria provided, single submitter clinical testing
Invitae RCV001087118 SCV000283867 benign Aortic valve disease 2 2020-09-07 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000299054 SCV000376502 likely benign Holt-Oram syndrome 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000515032 SCV000610894 likely benign not provided 2017-04-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620833 SCV000735178 benign Cardiovascular phenotype 2015-10-01 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000180104 SCV000920301 benign not specified 2018-01-15 criteria provided, single submitter clinical testing Variant summary: The TBX5 c.787G>A (p.Val263Met) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). Though a recent functional study demonstrated that the variant of interest could disrupts the TBX5-NuRD interaction (Waldron 2016), another study provided evidence that TBX5 activity may be extensively regulated through alternative splicing where the variant of interest would not affect isoforms lacking exon 9 (Yamak 2015). This variant was found in 403/276910 control chromosomes (with 1 homozygous occurrence), predominantly observed in the African subpopulation at a frequency of 0.012288 (295/24008). This frequency is about 2809 times the estimated maximal expected allele frequency of a pathogenic TBX5 variant (0.0000044), strong evidence that this is a benign polymorphism. The variant was reported in the literature in affected individuals, however without strong evidence for causality (Faria 2008, Bonachea 2014), i.e. no clear co-segregation could be demonstrated. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Mendelics RCV000299054 SCV001138832 uncertain significance Holt-Oram syndrome 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV000515032 SCV001845065 benign not provided 2020-10-19 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 18706711, 25260786)

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