ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.103939T>C (p.Tyr34647His)

gnomAD frequency: 0.00002  dbSNP: rs561869617
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001768651 SCV001992480 uncertain significance not provided 2019-02-08 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016; McVean et al., 2012; Exome Variant Server); Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001861083 SCV002182468 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 34647 of the TTN protein (p.Tyr34647His). This variant is present in population databases (rs561869617, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1305444). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is located in the M band of TTN (PMID: 25589632). Non-truncating variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002405294 SCV002673138 uncertain significance Cardiovascular phenotype 2019-12-30 criteria provided, single submitter clinical testing The p.Y25582H variant (also known as c.76744T>C), located in coding exon 185 of the TTN gene, results from a T to C substitution at nucleotide position 76744. The tyrosine at codon 25582 is replaced by histidine, an amino acid with 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.
Fulgent Genetics, Fulgent Genetics RCV002477935 SCV002797042 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 2021-09-29 criteria provided, single submitter clinical testing

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