ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.94828G>A (p.Ala31610Thr)

gnomAD frequency: 0.00002  dbSNP: rs141357723
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040812 SCV000064503 uncertain significance not specified 2012-05-04 criteria provided, single submitter clinical testing The Ala29042Thr variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. This variant has not been identified in a ve ry large and broad population by the NHLBI Exome Sequencing Project (http://evs. gs.washington.edu/EVS). This low frequency is consistent with a disease causing role but insufficient to establish this with confidence. Alanine (Ala) at positi on 29042 is not well conserved in evolution, suggesting that a change would be t olerated. However, this variant is located in the last bases of the exon, which is part of the 5? splice region. Computational tools predict a possible effect on splicing, though the accuracy of these tools is unknown. Other computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional i nformation is needed to fully assess the clinical significance of the Ala29042Th r variant
Eurofins Ntd Llc (ga) RCV000723743 SCV000114479 uncertain significance not provided 2013-09-30 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001171239 SCV001333943 uncertain significance Cardiomyopathy 2018-06-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002362654 SCV002661621 uncertain significance Cardiovascular phenotype 2019-10-02 criteria provided, single submitter clinical testing The p.A22545T variant (also known as c.67633G>A), located in coding exon 168 of the TTN gene, results from a G to A substitution at nucleotide position 67633. The amino acid change results in alanine to threonine at codon 22545, an amino acid with similar properties. This change occurs in the last base pair of coding exon 168, which makes it likely to have some effect on normal mRNA splicing. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, and is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. The nucleotide and amino acid positions are not well conserved in available vertebrate species, and threonine is the reference amino acid in other vertebrate species. In addition, the amino acid change is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002483019 SCV002781470 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 2021-11-17 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.