Submissions for variant NM_001271208.2(NEB):c.12770G>A (p.Arg4257His) (rs576918934)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000607026	SCV000718889	likely benign	not specified	2017-12-06	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000693401	SCV000821269	uncertain significance	Nemaline myopathy 2	2017-11-27	criteria provided, single submitter	clinical testing	This variant occurs in a region of NEB (Exons 82-105) consisting of three highly homologous 8-exon repeat units (exons 82-89, exons 90-97, exons 98-105). Sequence variants in this region can be detected, but this assay cannot determine which of the three repeat units is affected, and zygosity is often ambiguous. All variants in this region are reported relative to the exon 82-89 repeat. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with NEB-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc.	RCV000693401	SCV001460877	benign	Nemaline myopathy 2	2019-11-11	no assertion criteria provided	clinical testing