Submissions for variant NM_017739.4(POMGNT1):c.208G>A (p.Glu70Lys)

gnomAD frequency: 0.00004  dbSNP: rs201361648

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725149	SCV000334493	uncertain significance	not provided	2015-08-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000725149	SCV000620553	uncertain significance	not provided	2017-09-05	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the POMGNT1 gene. The E70K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E70K variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E70K 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. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is 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	RCV000695339	SCV000823831	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 70 of the POMGNT1 protein (p.Glu70Lys). This variant is present in population databases (rs201361648, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 282829). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POMGNT1 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.
Mendelics	RCV002248508	SCV002519199	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002518862	SCV003700637	uncertain significance	Inborn genetic diseases	2022-10-12	criteria provided, single submitter	clinical testing	The c.208G>A (p.E70K) alteration is located in exon 3 (coding exon 2) of the POMGNT1 gene. This alteration results from a G to A substitution at nucleotide position 208, causing the glutamic acid (E) at amino acid position 70 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000725149	SCV003811774	uncertain significance	not provided	2019-02-26	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001272277	SCV001454111	uncertain significance	Muscle eye brain disease	2020-01-12	no assertion criteria provided	clinical testing