ClinVar Miner

Submissions for variant NM_152263.4(TPM3):c.857A>C (p.Ter286Ser)

gnomAD frequency: 0.00001  dbSNP: rs199474720
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000707046 SCV000836126 likely pathogenic Congenital myopathy 4B, autosomal recessive; Congenital myopathy with fiber type disproportion 2023-10-11 criteria provided, single submitter clinical testing This sequence change disrupts the translational stop signal of the TPM3 mRNA. It is expected to extend the length of the TPM3 protein by 57 additional amino acid residues. This variant is present in population databases (rs199474720, gnomAD 0.009%). This protein extension has been observed in individuals with autosomal recessive nemaline myopathy and congenital fiber type disproportion (PMID: 12196661, 19953533). ClinVar contains an entry for this variant (Variation ID: 12447). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this protein extension affects TPM3 function (PMID: 12196661, 21357678). This variant results in an extension of the TPM3 protein. Other variant(s) that result in a similarly extended protein product (p.*286Lysext*57) have been observed in individuals with TPM3-related disease (PMID: 33124102). This suggests that these extensions may be clinically significant. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000013260 SCV000033507 pathogenic Congenital myopathy 4B, autosomal recessive 2008-03-01 no assertion criteria provided literature only
GeneReviews RCV000013260 SCV000058565 not provided Congenital myopathy 4B, autosomal recessive no assertion provided literature only
TPM3 homepage - Leiden Muscular Dystrophy pages RCV000128708 SCV000172348 not provided not provided no assertion provided not provided

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