ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.90991C>T (p.Pro30331Ser) (rs75022916)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618251 SCV000735460 uncertain significance Cardiovascular phenotype 2016-07-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000728236 SCV000855782 uncertain significance not provided 2017-07-17 criteria provided, single submitter clinical testing
GeneDx RCV000184964 SCV000237739 likely benign not specified 2017-11-24 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000697121 SCV000825715 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-06-20 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 30331 of the TTN protein (p.Pro30331Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs75022916, ExAC 0.07%). This variant has not been reported in the literature in individuals with TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 202973). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. This variant identified in the TTN gene is located in the A band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. 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.

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