Submissions for variant NM_002473.6(MYH9):c.2482T>C (p.Trp828Arg)

dbSNP: rs2146345102

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002226406	SCV002505348	likely pathogenic	Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss		criteria provided, single submitter	research
Genetics and Molecular Pathology, SA Pathology	RCV002226406	SCV004175651	likely pathogenic	Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss	2022-11-17	criteria provided, single submitter	clinical testing	The MYH9 c.2482T>C variant is classified as Likely Pathogenic (PS4_Moderate, PM2, PS3_supporting, PP2) The MYH9 c.2482T>C variant is a single nucleotide change in exon 20/41 of the MYH9 gene, which is predicted to change the amino acid tryptophan at position 828 in the protein to arginine. The variant has been reported in two patients with macrothrombocytopenia (PMID:29090586) (PS4_Moderate). This variant is absent from population databases (PM2). Immunofluorescence staining showed type III neutrophil inclusion body in one of the patients with the variant (PMID:29090586) (PS3_supporting). This is a missense variant in a constrained gene where missense variants are a common mechanism of disease and benign variation is rare (PP2). The variant has been reported as disease causing in the HGMD database (CM1723927). It has not been reported in dbSNP or ClinVar.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002254216	SCV002525479	pathogenic	Macrothrombocytopenia		no assertion criteria provided	research