Submissions for variant NM_005055.5(RAPSN):c.360G>T (p.Gln120His)

gnomAD frequency: 0.00002  dbSNP: rs780338213

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000326705	SCV000372472	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	RCV000378983	SCV000372473	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000803868	SCV000943755	uncertain significance	Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11	2022-02-03	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 120 of the RAPSN protein (p.Gln120His). This variant is present in population databases (rs780338213, gnomAD 0.007%). 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: 304981). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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	RCV002520727	SCV003659444	uncertain significance	Inborn genetic diseases	2022-11-10	criteria provided, single submitter	clinical testing	The c.360G>T (p.Q120H) alteration is located in exon 2 (coding exon 2) of the RAPSN gene. This alteration results from a G to T substitution at nucleotide position 360, causing the glutamine (Q) at amino acid position 120 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV003488518	SCV004236549	uncertain significance	not provided	2023-05-16	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001833443	SCV002089163	uncertain significance	Congenital myasthenic syndrome	2019-11-11	no assertion criteria provided	clinical testing