ClinVar Miner

Submissions for variant NM_139343.3(BIN1):c.925G>A (p.Glu309Lys)

gnomAD frequency: 0.00011  dbSNP: rs374565677
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000445206 SCV000532295 uncertain significance not provided 2016-10-14 criteria provided, single submitter clinical testing The E309K variant in the BIN1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E309K variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E309K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E309K as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001045898 SCV001209773 uncertain significance Myopathy, centronuclear, 2 2024-09-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 309 of the BIN1 protein (p.Glu309Lys). This variant is present in population databases (rs374565677, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BIN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 389673). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BIN1 protein function with a negative predictive value of 80%. 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.
Revvity Omics, Revvity RCV001045898 SCV003829891 uncertain significance Myopathy, centronuclear, 2 2019-09-13 criteria provided, single submitter clinical testing

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