Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000552911 | SCV000654052 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12; Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 12 | 2017-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with aspartic acid at codon 302 of the POMK protein (p.Val302Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. This variant is present in population databases (rs199756983, ExAC 0.01%). This variant was reported with a second truncating variant (p.Phe96fs) in an individual affected with autosomal recessive Walker Warburg Syndrome (PMID: 24925318). ClinVar contains an entry for this variant (Variation ID: 160349). Experimental studies have shown that this variant affects the kinase function of the POMK protein and does not allow for proper glycosylation of alpha-dystroglycan (PMID: 27879205). In summary, this variant is a rare missense change that has been reported to affect POMK protein function and reported in an affected individual. However, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| OMIM | RCV000148016 | SCV000195516 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 | 2014-11-01 | no assertion criteria provided | literature only |