Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000528327 | SCV000652586 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7; Autosomal recessive limb-girdle muscular dystrophy type 2U | 2022-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 231 of the ISPD protein (p.Asp231Glu). This variant is present in population databases (rs770257307, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with ISPD-related conditions. ClinVar contains an entry for this variant (Variation ID: 473156). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Gene |
RCV001570151 | SCV001794374 | likely benign | not provided | 2020-09-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004024226 | SCV003939306 | uncertain significance | not specified | 2023-04-17 | criteria provided, single submitter | clinical testing | The c.693C>A (p.D231E) alteration is located in exon 4 (coding exon 4) of the ISPD gene. This alteration results from a C to A substitution at nucleotide position 693, causing the aspartic acid (D) at amino acid position 231 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |