Submissions for variant NM_005055.5(RAPSN):c.364G>A (p.Gly122Arg)

gnomAD frequency: 0.00005  dbSNP: rs150756111

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001106664	SCV001263745	uncertain significance	Fetal akinesia deformation sequence 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001106665	SCV001263746	uncertain significance	Congenital myasthenic syndrome 11	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Fulgent Genetics, Fulgent Genetics	RCV002505680	SCV002803986	uncertain significance	Congenital myasthenic syndrome 11; Fetal akinesia deformation sequence 2	2021-12-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002556089	SCV003244170	uncertain significance	Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 122 of the RAPSN protein (p.Gly122Arg). This variant is present in population databases (rs150756111, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with RAPSN-related conditions. ClinVar contains an entry for this variant (Variation ID: 879296). 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 RAPSN 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.
Ambry Genetics	RCV002556090	SCV003705435	uncertain significance	Inborn genetic diseases	2021-08-12	criteria provided, single submitter	clinical testing	The c.364G>A (p.G122R) alteration is located in exon 2 (coding exon 2) of the RAPSN gene. This alteration results from a G to A substitution at nucleotide position 364, causing the glycine (G) at amino acid position 122 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV003490075	SCV004236546	uncertain significance	not provided	2023-08-07	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001279260	SCV001466343	uncertain significance	Congenital myasthenic syndrome	2020-04-14	no assertion criteria provided	clinical testing