Submissions for variant NM_017534.6(MYH2):c.5630T>C (p.Leu1877Pro)

dbSNP: rs2142289928

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV001733833	SCV001984823	likely pathogenic	Myopathy, proximal, and ophthalmoplegia	2020-07-23	criteria provided, single submitter	clinical testing	This variant has been previously reported as a de novo heterozygous change in one individual with distal and proximal muscle weakness, bulbar involvement, and ophthalmoplegia (PMID: 25529940). It is absent from the gnomAD population database and thus is presumed to be rare. The c.5630T>C (p.Leu1877Pro) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.5630T>C (p.Leu1877Pro) variant is classified as Likely Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001733833	SCV002102422	likely pathogenic	Myopathy, proximal, and ophthalmoplegia	2024-10-01	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV001733833	SCV004013905	pathogenic	Myopathy, proximal, and ophthalmoplegia	2023-02-17	criteria provided, single submitter	clinical testing	PS2, PM2, PP3, PP5