Submissions for variant NM_001271208.2(NEB):c.23246G>A (p.Arg7749Gln) (rs200963111)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000246953	SCV000718940	likely benign	not specified	2017-05-03	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	RCV000526264	SCV000640718	uncertain significance	Nemaline myopathy 2	2017-07-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 7749 of the NEB protein (p.Arg7749Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs200963111, ExAC 0.2%) but has not been reported in the literature in individuals with a NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 257796). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Unavailable"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics	RCV000246953	SCV000307312	likely benign	not specified		criteria provided, single submitter	clinical testing