Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002990861 | SCV003705700 | uncertain significance | Inborn genetic diseases | 2022-11-08 | criteria provided, single submitter | clinical testing | The c.1492T>C (p.F498L) alteration is located in exon 17 (coding exon 17) of the BIN1 gene. This alteration results from a T to C substitution at nucleotide position 1492, causing the phenylalanine (F) at amino acid position 498 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV003143567 | SCV003829888 | uncertain significance | Myopathy, centronuclear, 2 | 2019-06-25 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003143567 | SCV004685652 | uncertain significance | Myopathy, centronuclear, 2 | 2023-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 498 of the BIN1 protein (p.Phe498Leu). This variant is present in population databases (rs368238742, gnomAD 0.01%). 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: 2367119). 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 BIN1 protein function. 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. |