ClinVar Miner

Submissions for variant NM_152263.4(TPM3):c.43G>C (p.Asp15His)

dbSNP: rs1553251644
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center of Genomic medicine, Geneva, University Hospital of Geneva RCV000503601 SCV000598150 likely pathogenic Congenital myopathy with fiber type disproportion 2016-09-26 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000727596 SCV000854845 uncertain significance not provided 2018-07-17 criteria provided, single submitter clinical testing
Invitae RCV000806717 SCV000946731 likely pathogenic Congenital myopathy 4B, autosomal recessive; Congenital myopathy with fiber type disproportion 2019-01-07 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 15 of the TPM3 protein (p.Asp15His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with congenital hypotonia and muscle weakness (Invitae). ClinVar contains an entry for this variant (Variation ID: 437430). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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