Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693712 | SCV000821593 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7; Autosomal recessive limb-girdle muscular dystrophy type 2U | 2018-02-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with tryptophan at codon 54 of the ISPD protein (p.Gly54Trp). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and tryptophan. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with ISPD-related disease. 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 C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. A different missense substitution at this codon (p.Gly54Ala) has been reported as homozygous in individuals affected with muscular dystrophy-dystroglycanopathy (PMID: 23390185). |