Submissions for variant NM_152263.4(TPM3):c.401G>A (p.Arg134Gln)

dbSNP: rs769493959

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002021590	SCV002315563	uncertain significance	Congenital myopathy 4B, autosomal recessive; Congenital myopathy with fiber type disproportion	2023-08-31	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. 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 not expected to disrupt TPM3 protein function. ClinVar contains an entry for this variant (Variation ID: 1518234). This variant has not been reported in the literature in individuals affected with TPM3-related conditions. This variant is present in population databases (rs769493959, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 134 of the TPM3 protein (p.Arg134Gln).
Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire	RCV004587292	SCV005038512	likely pathogenic	Centronuclear myopathy	2024-03-01	criteria provided, single submitter	research	PM2+PM6+PP2+PP3