ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.89711G>A (p.Arg29904His)

gnomAD frequency: 0.00005  dbSNP: rs397517744
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040760 SCV000064451 uncertain significance not specified 2012-03-22 criteria provided, single submitter clinical testing The Arg27336His variant (TTN) has not been reported in the literature but has be en identified in one individual with DCM tested by our laboratory. Arginine (Arg ) at position 27336 is conserved in evolutionarily distant species, increasing t he likelihood that a change would not be tolerated. Computational predictions ar e inconsistent (AlignGVGD = benign, SIFT = pathogenic), though their accuracy is unknown. Additional data is required to assess the clinical significance of thi s variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000231353 SCV000286900 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-10-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002362638 SCV002660778 uncertain significance Cardiovascular phenotype 2019-02-14 criteria provided, single submitter clinical testing The p.R20839H variant (also known as c.62516G>A), located in coding exon 162 of the TTN gene, results from a G to A substitution at nucleotide position 62516. The arginine at codon 20839 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available 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.
Fulgent Genetics, Fulgent Genetics RCV002504914 SCV002814334 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 2021-07-13 criteria provided, single submitter clinical testing
New York Genome Center RCV003227626 SCV003925348 uncertain significance Dilated cardiomyopathy 1G; Hypertrophic cardiomyopathy 9 2022-04-08 criteria provided, single submitter clinical testing The c.89711G>A (p. Arg29904His) missense variant in the TTN gene identified in exon 335 (of 363) of this individual has not been reported in affected individuals in the literature. The variant has 0.00003943 allele frequency in the gnomAD (v3.1.2) database (6 out of 152164 heterozygous alleles, no homozygotes)suggesting it is not a common benign variant in the populations represented in that database. This variant is reported as a variant of uncertain significance in the ClinVar database (Variation ID: 47491). The variant affects a conserved residue (Arg29904) located in the Ig like and fibronectin type III domain of A-Band of TTN protein (PMID: 29238064, Uniprot and http://cardiodb.org/titin/). In silico predictions are moderately in favor of damaging effect for p. Arg29904His (CADD score =34,REVEL score = 0.486). Based on the available evidence, the c.89711G>A (p. Arg29904His) missense variant identified in the TTN gene is reported as a Variant of Uncertain Significance.

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