ClinVar Miner

Submissions for variant NM_005055.5(RAPSN):c.549_553dup (p.Phe185fs)

dbSNP: rs786200904
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002512910 SCV003439865 pathogenic Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11 2022-11-03 criteria provided, single submitter clinical testing This premature translational stop signal has been observed in individual(s) with congenital myasthenic syndrome (PMID: 11791205). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this premature translational stop signal affects RAPSN function (PMID: 11791205). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 8048). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe185Cysfs*20) in the RAPSN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAPSN are known to be pathogenic (PMID: 17686188).
PreventionGenetics, part of Exact Sciences RCV004532313 SCV004116118 likely pathogenic RAPSN-related disorder 2022-11-15 criteria provided, single submitter clinical testing The RAPSN c.549_553dup5 variant is predicted to result in a frameshift and premature protein termination (p.Phe185Cysfs*20). This variant was reported in the compound heterozygous state in patients with congenital myasthenic syndrome (variant referred to as 553ins5 in Patient 4, Ohno et al. 2002. PubMed ID: 11791205; variant referred to as 551ins5 in patients 2 and 5, Burke et al. 2003. PubMed ID: 14504330). Functional analysis showed that this variant impacted recruitment of the acetylcholine receptor to rapsyn clusters (Ohno et al. 2002. PubMed ID: 11791205). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in RAPSN are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Baylor Genetics RCV004566695 SCV005054078 pathogenic Fetal akinesia deformation sequence 2 2024-03-10 criteria provided, single submitter clinical testing
OMIM RCV000008514 SCV000028722 pathogenic Congenital myasthenic syndrome 11 2002-04-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.