Submissions for variant NM_005055.5(RAPSN):c.490C>T (p.Arg164Cys)

gnomAD frequency: 0.00002  dbSNP: rs104894294

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000415079	SCV000492842	likely pathogenic	Myopathy	2015-05-05	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000008520	SCV001370162	pathogenic	Congenital myasthenic syndrome 11	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS3,PM2,PM3,PP4,PP3.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001343279	SCV001537249	pathogenic	Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11	2023-11-28	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 164 of the RAPSN protein (p.Arg164Cys). This variant is present in population databases (rs104894294, gnomAD 0.005%). This missense change has been observed in individuals with congenital myasthenic syndrome and/or limb-girdle weakness (PMID: 16931511, 32070632, 32528171, 34106991). ClinVar contains an entry for this variant (Variation ID: 8054). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RAPSN protein function. Experimental studies have shown that this missense change affects RAPSN function (PMID: 16931511). This variant disrupts the p.Arg164 amino acid residue in RAPSN. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000008520	SCV002053764	pathogenic	Congenital myasthenic syndrome 11		criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003466839	SCV004206078	likely pathogenic	Fetal akinesia deformation sequence 2	2024-02-06	criteria provided, single submitter	clinical testing
OMIM	RCV000008520	SCV000028728	pathogenic	Congenital myasthenic syndrome 11	2006-10-10	no assertion criteria provided	literature only