Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000725596 | SCV000338011 | pathogenic | not provided | 2017-04-25 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000471321 | SCV000548504 | pathogenic | Walker-Warburg congenital muscular dystrophy | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change disrupts the translational stop signal of the FKRP mRNA. It is expected to extend the length of the FKRP protein by 21 additional amino acid residues. This variant is present in population databases (rs104894682, gnomAD 0.0009%). This protein extension has been observed in individuals with limb girdle muscular dystrophy (PMID: 10838249, 12707439, 15060126, 18671187). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4223). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic. |
Genetic Services Laboratory, |
RCV000501528 | SCV000594787 | likely pathogenic | Muscular dystrophy-dystroglycanopathy | 2017-04-13 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222339 | SCV002500248 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy | 2022-03-01 | criteria provided, single submitter | clinical testing | Variant summary: FKRP c.1486T>A (p.X496ArgextX21) changes the termination codon and is predicted to lead to an extended protein with additional amino acids added to the normal C-terminus. The variant allele was found at a frequency of 8.1e-06 in 245964 control chromosomes (gnomAD). c.1486T>A has been reported in the literature in multiple individuals affected with Limb-Girdle Muscular Dystrophy and vacuolar myopathy (examples: Driss_2003, Kefi_2008, Mair_2020, Walter_FKRP_2004). The variant also seggregated with disease. These data indicate that the variant is very likely to be associated with disease. Driss_2003 demonstrated that this variant reduced alpha dystroglycan and laminin levels in isolated muscle protein immmunoblots. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic (n=4) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. |
OMIM | RCV000004444 | SCV000024617 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2003-04-22 | no assertion criteria provided | literature only | |
Natera, |
RCV000004444 | SCV002091359 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2020-09-09 | no assertion criteria provided | clinical testing |