ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.40652del (p.Pro13551fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV003226064 SCV003922165 likely pathogenic Early-onset myopathy with fatal cardiomyopathy 2023-05-02 criteria provided, single submitter curation The heterozygous p.Pro13551GlnfsTer47 variant in TTN was identified by our study, in the compound heterozygous state with a likely pathogenic variant (NC_000002.12:g.178530764dup), in one individual with Salih myopathy. This individual also carried a likely pathogenic variant (NC_000002.12:g.178530764dup); however, the phase of these variants is unknown at this time. The p.Pro13551GlnfsTer47 variant in TTN has not been previously reported in individuals with Salih myopathy. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 13551 and leads to a premature termination codon 47 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the TTN gene is an established disease mechanism in autosomal recessive Salih myopathy. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for Salih myopathy. ACMG/AMP Criteria applied: PVS1, PM2_Supporting (Richards 2015).

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