Submissions for variant NM_005055.5(RAPSN):c.149_153delinsAGATGGGCCGCTACAAGGAGATGG (p.Val50fs)

dbSNP: rs1131691986

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493313	SCV000583280	pathogenic	not provided	2017-05-25	criteria provided, single submitter	clinical testing	The c.149_153delTCACAins24 pathogenic variant in the RAPSN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.149_153delTCACAins24 variant causes a frameshift starting with codon Valine 50, changes this amino acid to a Glutamic acid residue, and creates a premature Stop codon at position 114 of the new reading frame, denoted p.Val50GlufsX114. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.149_153delTCACAins24 variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.149_153delTCACAins24 as a pathogenic variant.
Center for Reproductive Medicine, Peking University Third Hospital	RCV001257395	SCV001433923	pathogenic	Hydrops fetalis	2019-10-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002298624	SCV002598807	pathogenic	Congenital myasthenic syndrome	2022-09-20	criteria provided, single submitter	clinical testing	Variant summary: RAPSN c.149_153delinsAGATGGGCCGCTACAAGGAGATGG (p.Val50GlufsX114) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250662 control chromosomes (gnomAD). c.149_153delins24 has been reported in the literature as a biallelic genotype in two families with repeat occurrences of Hydrops Fetalis/Fetal Akinesia (Guo_2020, Zhou_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000493313	SCV003916716	pathogenic	not provided	2022-03-01	criteria provided, single submitter	clinical testing	RAPSN: PVS1, PM2