ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1387A>G (p.Asn463Asp) (rs121908110)

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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000178346 SCV000230411 pathogenic not provided 2016-06-30 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000194089 SCV000247379 pathogenic Muscular dystrophy 2015-05-15 criteria provided, single submitter clinical testing
Invitae RCV000540601 SCV000630832 pathogenic Walker-Warburg congenital muscular dystrophy 2019-09-18 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 463 of the FKRP protein (p.Asn463Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs121908110, ExAC 0.2%). This variant has been reported in the homozygous state in 2 individuals of Mexican ancestry affected with congenital muscular dystrophy (PMID: 17336067) and on the opposite chromosome (in trans) from a pathogenic FKRP variant in an individual affected with limb girdle muscular dystrophy (Invitae database). This variant has also been reported to segregate with muscular dystrophy in an affected family (Invitae database). ClinVar contains an entry for this variant (Variation ID: 4235). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change that has been reported in several affected individuals and has been reported to segregate with disease in affected families. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004457 SCV000024630 pathogenic Congenital muscular dystrophy-dystroglycanopathy without mental retardation, type B5 2007-04-01 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.