ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.44987G>A (p.Arg14996His)

gnomAD frequency: 0.00003  dbSNP: rs762128685
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000227516 SCV000286670 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-06-19 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000733705 SCV000732045 uncertain significance not provided 2022-05-04 criteria provided, single submitter clinical testing The p.Arg12428His variant in TTN has been reported in at least 1 individual with HCM and LVNC (Mazzarotto 2020 PMID: 31983221, Mazzarotto 2021 PMID: 33500567, LMM data). It has also been reported by other clinical laboratories in ClinVar (Variation ID: 238783) and has been identified in 0.004% (5/112032) of European chromosomes by (gnomAD, http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Arg12428His variant is uncertain. ACMG/AMP Criteria applied: BP4.
Eurofins Ntd Llc (ga) RCV000733705 SCV000861798 uncertain significance not provided 2018-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000733705 SCV001793274 likely benign not provided 2020-10-07 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 31983221)
Ambry Genetics RCV002399818 SCV002713950 uncertain significance Cardiovascular phenotype 2019-11-21 criteria provided, single submitter clinical testing The p.R5931H variant (also known as c.17792G>A), located in coding exon 71 of the TTN gene, results from a G to A substitution at nucleotide position 17792. The arginine at codon 5931 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well 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.
Revvity Omics, Revvity RCV000733705 SCV003821803 uncertain significance not provided 2023-08-11 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004734883 SCV005366577 uncertain significance TTN-related disorder 2024-06-11 no assertion criteria provided clinical testing The TTN c.44987G>A variant is predicted to result in the amino acid substitution p.Arg14996His. This variant has been reported in at least one individual with dilated cardiomyopathy (Table S3, Mazzarotto et al. 2020. PubMed ID: 31983221) and left ventricular noncompaction (Table S2, Mazzarotto et al. 2021. PubMed ID: 33500567). This variant is reported in 0.0045% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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