Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002010797 | SCV002296458 | likely pathogenic | Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 | 2021-09-02 | criteria provided, single submitter | clinical testing | This variant is also known as p.Pro298Leu. This missense change has been observed in individual(s) with Paget's disease of the bone (PMID: 28389692). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 310 of the HNRNPA2B1 protein (p.Pro310Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects HNRNPA2B1 function (PMID: 29358076). |