# Re-evaluating the MYH9 p.I1816V variant in a patient with atypical clinical presentation

## TL;DR

A 16-year-old boy with a rare MYH9 gene variant shows atypical symptoms, challenging the understanding of how this genetic change affects health.

## Contribution

This case highlights the difficulty of interpreting rare genetic variants when clinical features are absent or inconsistent.

## Key findings

- The patient had a MYH9 p.I1816V variant but no typical MYH9-RD features like macrothrombocytopenia or leukocyte inclusions.
- The variant is more common in East Asian populations and is predicted to be benign by computational tools.
- The case underscores the need for cautious interpretation of rare genetic variants in clinical settings.

## Abstract

MYH9-related disease (MYH9-RD) is an autosomal dominant disorder typically characterized by macrothrombocytopenia, leukocyte inclusion bodies, and variable non-hematologic manifestations such as hearing loss and nephropathy. We herein describe a 16-year-old boy presenting with persistent proteinuria and biopsy-proven membranous nephropathy with focal segmental sclerosis. Genetic testing identified a rare MYH9 variant (p.I1816V), previously reported in association with Epstein syndrome. However, the patient had normal platelet counts, no leukocyte inclusions, and no abnormalities in non-muscle myosin heavy chain IIA (NMMHC-IIA) expression in neutrophils or podocytes. Although globally rare, the p.I1816V variant is more frequent in East Asian populations and is predicted to be benign by multiple in silico tools. This case illustrates the challenges of interpreting rare variants in the absence of supportive clinical findings and highlights the need for cautious evaluation in the era of next-generation sequencing.

The online version contains supplementary material available at 10.1007/s00467-025-07059-8.