ClinVar Miner

Submissions for variant NM_152263.4(TPM3):c.11C>T (p.Ala4Val)

dbSNP: rs199474711
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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 RCV001237893 SCV001410679 uncertain significance Congenital myopathy 4B, autosomal recessive; Congenital myopathy with fiber type disproportion 2022-09-12 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects TPM3 function (PMID: 30768849). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 42113). This missense change has been observed in individuals with clinical features of congenital myopathy (PMID: 19953533; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 4 of the TPM3 protein (p.Ala4Val).
GeneDx RCV000128693 SCV001989409 uncertain significance not provided 2019-09-24 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Identified in multiple affected individuals in a family with congenital fiber type disproportion in published literature (Lawlor et al., 2010); This variant is associated with the following publications: (PMID: 19953533)
GeneReviews RCV000034941 SCV000058556 not provided Congenital myopathy with fiber type disproportion no assertion provided literature only
TPM3 homepage - Leiden Muscular Dystrophy pages RCV000128693 SCV000172333 not provided not provided no assertion provided not provided

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