Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040922 | SCV000064613 | uncertain significance | not specified | 2012-07-24 | criteria provided, single submitter | clinical testing | The Asn31645Ser variant in TTN has been identified in 1/8276 European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS/). This could represent a presymptomatic individual. Computational analyses (biochemical amino acid properties, conservation, AlignGV GD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the clinical s ignificance of the Asn31645Ser variant. |
Invitae | RCV000642696 | SCV000764383 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 34213 of the TTN protein (p.Asn34213Ser). This variant is present in population databases (rs375332499, gnomAD 0.003%). This missense change has been observed in individual(s) with infantile dilated cardiomyopathy (PMID: 24503780). This variant is also known as c.94934A>G (p.Asn31645Ser). ClinVar contains an entry for this variant (Variation ID: 47653). 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). 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. |
Revvity Omics, |
RCV003137573 | SCV003826663 | uncertain significance | not provided | 2019-03-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040922 | SCV004223619 | uncertain significance | not specified | 2023-11-09 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.94934A>G (p.Asn31645Ser) results in a conservative amino acid change located in the M-Band domain of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249038 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.94934A>G has been reported in the literature in one individual affected with Dilated Cardiomyopathy (Pugh_2014). The report does not provide unequivocal conclusions about association of the variant with Limb-Girdle Muscular Dystrophy, Type 2J. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 24503780). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |