ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.12821G>A (p.Ser4274Asn)

gnomAD frequency: 0.00006  dbSNP: rs200348414
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172417 SCV000055077 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000217501 SCV000272864 uncertain significance not specified 2015-08-21 criteria provided, single submitter clinical testing The p.Ser4036Asn variant in TTN has been identified by our laboratory in one Cau casian adult with DCM and NSVT who carried a second likely pathogenic variant. I t has also been identified in 9/66308 European chromosomes by the Exome Aggregat ion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200348414). Comput ational prediction tools and conservation analysis are limited or unavailable fo r this variant. In summary, the clinical significance of the p.Ser4036Asn varian t is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000544990 SCV000642667 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-08-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620036 SCV000736609 uncertain significance Cardiovascular phenotype 2019-12-16 criteria provided, single submitter clinical testing The p.S3911N variant (also known as c.11732G>A), located in coding exon 44 of the TTN gene, results from a G to A substitution at nucleotide position 11732. The serine at codon 3911 is replaced by asparagine, an amino acid with highly similar properties. This alteration (described as NM_133378.4:c.10361-2052G>A) has been reported as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is not well conserved in available vertebrate species, and asparagine is the reference amino acid in other vertebrate species. In addition, this alteration 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.
GeneDx RCV000172417 SCV001796770 likely benign not provided 2019-12-18 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000172417 SCV004229373 uncertain significance not provided 2023-07-14 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org). This variant is in a coding region of the longest isoform of TTN, inferred model NM_001267550.1, and in the cardiac muscle isoform (NM_001256850.1); however, it is in a non-coding region of the main skeletal isoform (NM_133378.4). Computational tools predict that this variant is not damaging.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003486720 SCV004239819 likely benign Cardiomyopathy 2023-05-16 criteria provided, single submitter clinical testing

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