ClinVar Miner

Submissions for variant NM_005876.5(SPEG):c.8965_8989dup (p.Val2997fs)

dbSNP: rs1575201712
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001004855 SCV001164332 likely pathogenic Myopathy, centronuclear, 5 2018-12-03 criteria provided, single submitter research The heterozygous p.Val2997GlyfsTer52 variant in SPEG was identified by our study in the compound heterozygous state, with another pathogenic variant, in one individual with Centronuclear Myopathy. This variant was absent from large population studies. A knock-out mouse model for the SPEG gene has a phenotype that matches Centronuclear Myopathy and at least two loss of function variants across multiple exons have been reported in association with Centronuclear Myopathy in the literature (PMID: 19118250, 25087613). This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 2997 and leads to a premature termination codon 52 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the SPEG gene is a moderately established disease mechanism in autosomal recessive Centronuclear Myopathy, and this is a loss of function variant. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic.
Revvity Omics, Revvity RCV001004855 SCV002021919 pathogenic Myopathy, centronuclear, 5 2020-09-24 criteria provided, single submitter clinical testing

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