Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001379323 | SCV001577109 | pathogenic | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11 | 2023-09-21 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1067929). Disruption of this splice site has been observed in individual(s) with clinical features of congenital myasthenic syndrome (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects a donor splice site in intron 2 of the RAPSN gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RAPSN are known to be pathogenic (PMID: 17686188). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Illumina Laboratory Services, |
RCV001563594 | SCV001786568 | likely pathogenic | Congenital myasthenic syndrome 11 | 2020-12-04 | criteria provided, single submitter | clinical testing | The RAPSN c.531+1G>T variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt the normal gene product. A literature search was performed for the gene, and cDNA change. No publications were found based on this search. This variant is found at a frequency of 0.000059 in the Latino population of the Genome Aggregation Database, but this is based on two alleles in a region of good sequence coverage, so the variant is presumed to be rare. Based on the potential impact of splice donor variants and application of ACMG criteria, the c.531+1G>T variant is classified as likely pathogenic for congenital myasthenic syndrome. |
Baylor Genetics | RCV003462961 | SCV004206089 | likely pathogenic | Fetal akinesia deformation sequence 2 | 2023-09-14 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005050365 | SCV005684653 | likely pathogenic | Congenital myasthenic syndrome 11; Fetal akinesia deformation sequence 2 | 2024-04-03 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001826152 | SCV002089157 | likely pathogenic | Congenital myasthenic syndrome | 2020-10-28 | no assertion criteria provided | clinical testing |