ClinVar Miner

Submissions for variant NM_005681.4(TAF1A):c.1021G>A (p.Gly341Arg)

gnomAD frequency: 0.00004  dbSNP: rs765321518
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV002261375 SCV002540789 uncertain significance Primary dilated cardiomyopathy criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003487538 SCV004238014 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing
Columbia University Laboratory of Personalized Genomic Medicine, Columbia University Medical Center RCV001615034 SCV001775486 uncertain significance Cardiomyopathy, familial restrictive, 6 2021-07-30 no assertion criteria provided clinical testing The paternally inherited c.1021G>A, p.Gly341Arg variant in the TAF1A gene in this affected child is a missense variant, which results in a substitution of Glycine residue to Arginine at position 341/451 of the protein, predicted to be damaging by multiple in silico prediction tools (SIFT and PROVEAN). This variant is rare from the gnomAD database with allele frequency 0.00002797 (7/250252 heterozygotes, 0 homozygote) indicating that it is not a common benign occurrence in the populations represented in the database. This variant has been previously reported in two cardiomyopathy sisters (2-3 years old) in compound heterozygous state with another missense variant in the TAF1A gene (PMID: 28472305). TAF1A encodes a TATA box-binding protein-associated factor which is required for RNA polymerase I to synthesize ribosomal RNA. In one study, the TAF1A gene specific subcellular phenotype was identified in approximately 50% of the cardiomyocytes of the affected sisters and was absent in pediatric normal and DCM controls. In a functional study of this gene, TAF1A-/- zebrafish recapitulate a heart failure phenotype (PMID: 28472305). However, since only one pediatric cardiomyopathy family has been reported with compound heterozygous TAF1A variants, the gene-disease association for TAF1A with pediatric cardiomyopathy remains uncertain. Given these evidences, TAF1A is a gene of unknown significance and therefore the c.1021G>A, p.Gly341Arg variant is classified as variant of unknown significance.

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