Submissions for variant NM_001164508.2(NEB):c.19543C>T (p.Arg6515Cys)

gnomAD frequency: 0.00002  dbSNP: rs765363585

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000521082	SCV000618650	uncertain significance	not provided	2017-06-29	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the NEB gene. The R6515C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R6515C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R6515C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. 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. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with nemaline myopathy (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001243032	SCV001416162	likely benign	Nemaline myopathy 2	2024-01-29	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001243032	SCV001440702	uncertain significance	Nemaline myopathy 2	2019-01-01	criteria provided, single submitter	clinical testing	This variant was identified as compound heterozygous.
Natera, Inc.	RCV001243032	SCV002084122	uncertain significance	Nemaline myopathy 2	2019-11-11	no assertion criteria provided	clinical testing