Submissions for variant NM_001164508.2(NEB):c.11341C>T (p.Arg3781Trp)

gnomAD frequency: 0.00005  dbSNP: rs533027587

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520790	SCV000621664	uncertain significance	not provided	2017-10-17	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the NEB gene. The R3781W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R3781W variant is observed in 44/18858 (0.2%) alleles from individuals of East Asian background, in large population cohorts (Lek et al., 2016). The R3781W 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. Additionally, this substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. 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	RCV000768442	SCV001019184	likely benign	Nemaline myopathy 2	2024-01-31	criteria provided, single submitter	clinical testing
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768442	SCV000899202	likely pathogenic	Nemaline myopathy 2		no assertion criteria provided	case-control