Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000760355 | SCV000226310 | pathogenic | not provided | 2014-03-20 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000760355 | SCV000890215 | pathogenic | not provided | 2018-08-21 | criteria provided, single submitter | clinical testing | The R514X nonsense variant in the POMT1 gene has been reported previously in the homozygous state in an individual with a clinical diagnosis of Walker-Warburg syndrome (Yis et al., 2007). The R514X variant has also been reported along with a second POMT1 variant in unrelated individuals with congenital muscular dystrophy, microcephaly, and intellectual disability with variable additional findings (D'Amico et al., 2006; van Reeuwijk et al., 2006). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R514X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R514X as a pathogenic variant. |
Invitae | RCV001851614 | SCV002231823 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg514*) in the POMT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMT1 are known to be pathogenic (PMID: 12369018, 15637732, 16575835). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with muscular dystrophy-dystroglycanopathy (PMID: 16717220, 31311558). This variant is also known as p.Arg541*. ClinVar contains an entry for this variant (Variation ID: 3245). 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. |
OMIM | RCV002286390 | SCV000023559 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 | 2006-05-01 | no assertion criteria provided | literature only |