Submissions for variant NM_005476.7(GNE):c.1651A>G (p.Ile551Val)

gnomAD frequency: 0.00008  dbSNP: rs754313408

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000267828	SCV000342836	uncertain significance	not provided	2016-06-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000693160	SCV000821016	uncertain significance	GNE myopathy; Sialuria	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 582 of the GNE protein (p.Ile582Val). This variant is present in population databases (rs754313408, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 288664). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Revvity Omics, Revvity	RCV000267828	SCV003815037	uncertain significance	not provided	2019-08-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000267828	SCV004698516	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing	GNE: PM2
GeneDx	RCV000267828	SCV005383099	uncertain significance	not provided	2024-01-25	criteria provided, single submitter	clinical testing	Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24796702)
Natera, Inc.	RCV001835760	SCV002075635	uncertain significance	GNE myopathy	2020-02-13	no assertion criteria provided	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV001835760	SCV004228946	not provided	GNE myopathy		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 07-24-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
PreventionGenetics, part of Exact Sciences	RCV004748698	SCV005353052	uncertain significance	GNE-related disorder	2024-03-14	no assertion criteria provided	clinical testing	The GNE c.1744A>G variant is predicted to result in the amino acid substitution p.Ile582Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.