Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000435212 | SCV000523541 | uncertain significance | not specified | 2016-02-29 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the BIN1 gene. The V372M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,300 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 V372M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV001064060 | SCV001228933 | uncertain significance | Myopathy, centronuclear, 2 | 2023-04-24 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 383228). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 372 of the BIN1 protein (p.Val372Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with BIN1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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, |
RCV001064060 | SCV003829878 | uncertain significance | Myopathy, centronuclear, 2 | 2019-05-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004022372 | SCV004911925 | uncertain significance | Inborn genetic diseases | 2024-02-05 | criteria provided, single submitter | clinical testing | The c.1114G>A (p.V372M) alteration is located in exon 12 (coding exon 12) of the BIN1 gene. This alteration results from a G to A substitution at nucleotide position 1114, causing the valine (V) at amino acid position 372 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |