ClinVar Miner

Submissions for variant NM_139343.3(BIN1):c.461G>A (p.Arg154Gln)

dbSNP: rs267606681
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000008798 SCV000930065 likely pathogenic Myopathy, centronuclear, 2 2019-01-08 criteria provided, single submitter curation This variant is interpreted as a Likely pathogenic for Myopathy, centronuclear, 2 autosomal recessive. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3 : Well-established functional studies show a deleterious effect (PMID:24755653). PP3 : Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM1 : Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation.
Labcorp Genetics (formerly Invitae), Labcorp RCV000008798 SCV001375361 uncertain significance Myopathy, centronuclear, 2 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 154 of the BIN1 protein (p.Arg154Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with centronuclear myopathy (PMID: 20142620). ClinVar contains an entry for this variant (Variation ID: 8300). 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 BIN1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects BIN1 function (PMID: 24755653, 25262827). 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.
OMIM RCV000008798 SCV000029008 pathogenic Myopathy, centronuclear, 2 2010-02-09 no assertion criteria provided literature only

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