ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.10303+2T>C (rs371596417)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619220 SCV000737081 likely pathogenic Cardiovascular phenotype 2016-04-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,Rarity in general population databases (dbsnp, esp, 1000 genomes),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000733858 SCV000861960 uncertain significance not provided 2018-06-25 criteria provided, single submitter clinical testing
Invitae RCV000459587 SCV000542520 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-04-17 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 44 of the TTN gene. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs371596417, ExAC 0.002%). This variant has not been reported in the literature in individuals with TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 404786). This variant identified in the TTN gene is located in the I band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. In summary, although this is a novel truncating variant, truncating variants in this region of the TTN gene have been shown to be highly prevalent in the TTN gene in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating mutations in this region have also been reported to cause autosomal recessive congenital myopathy (PMID: 23975875). Therefore without additional functional and/or genetic data, this variant has been classified as a Variant of Uncertain Significance.

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