Submissions for variant NM_017739.4(POMGNT1):c.793C>T (p.Arg265Cys)

gnomAD frequency: 0.00001  dbSNP: rs774752168

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome-Nilou Lab	RCV001578925	SCV001806284	uncertain significance	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3	2021-07-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001578926	SCV001806285	uncertain significance	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3	2021-07-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001578927	SCV001806286	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2O	2021-07-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001578928	SCV001806287	uncertain significance	Retinitis pigmentosa 76	2021-07-22	criteria provided, single submitter	clinical testing
3billion	RCV001578925	SCV002058517	uncertain significance	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3	2022-01-03	criteria provided, single submitter	clinical testing	The variant observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000008, PM2_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.776, PP3_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Invitae	RCV001866087	SCV002214502	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3	2022-07-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 265 of the POMGNT1 protein (p.Arg265Cys). This variant is present in population databases (rs774752168, gnomAD 0.003%). 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: 1209698). 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.