ClinVar Miner

Submissions for variant NM_003289.4(TPM2):c.382A>G (p.Lys128Glu)

dbSNP: rs1563929143
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000700134 SCV000828876 likely pathogenic Arthrogryposis, distal, type 1A 2023-10-09 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 128 of the TPM2 protein (p.Lys128Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant congenital myopathy (PMID: 24214167, 24692096). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 577391). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TPM2 protein function. 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.
GeneDx RCV002221578 SCV002498871 likely pathogenic not provided 2021-10-05 criteria provided, single submitter clinical testing Previously reported in an individual with congenital myopathy; additional clinical information and segregation data not provided (Savarese et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23886664, 25214167, 24692096)

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