Submissions for variant NM_004287.5(GOSR2):c.430G>T (p.Gly144Trp)

gnomAD frequency: 0.00009  dbSNP: rs387906881

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478768	SCV000567582	pathogenic	not provided	2023-02-15	criteria provided, single submitter	clinical testing	Observed with a second variant on the opposite allele (in trans) in a patient in published literature (Larsen et al., 2018) with hypotonia, progressive muscle weakness, seizures, and -dystroglycan hypoglycosylation; Published functional studies demonstrate a damaging effect (Praschberger et al., 2017; Volker et al., 2017); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27342741, 21549339, 28978487, 28982678, 27618868, 24458321, 25326637, 23449775, 29431110, 28264719, 29855340, 31692161, 30363482, 32105965, 33639315)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001068291	SCV001233394	pathogenic	Progressive myoclonic epilepsy	2024-10-27	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 144 of the GOSR2 protein (p.Gly144Trp). This variant is present in population databases (rs387906881, gnomAD 0.01%). This missense change has been observed in individuals with progressive myoclonic epilepsy (PMID: 21549339, 23449775). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30406). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects GOSR2 function (PMID: 21549339, 28982678). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000478768	SCV001500130	pathogenic	not provided	2020-09-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000023359	SCV002811597	pathogenic	Progressive myoclonic epilepsy type 6	2021-08-06	criteria provided, single submitter	clinical testing
OMIM	RCV000023359	SCV000044650	pathogenic	Progressive myoclonic epilepsy type 6	2014-01-01	no assertion criteria provided	literature only
GenomeConnect, ClinGen	RCV000509417	SCV000607038	not provided	Muscular dystrophy		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000023359	SCV000733691	pathogenic	Progressive myoclonic epilepsy type 6		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000478768	SCV001932184	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000478768	SCV001955380	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000478768	SCV001976064	pathogenic	not provided		no assertion criteria provided	clinical testing
OMIM	RCV002472356	SCV002769714	pathogenic	Muscular dystrophy, congenital, with or without seizures	2014-01-01	no assertion criteria provided	literature only