Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000728823 | SCV000856440 | uncertain significance | not provided | 2017-08-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002233734 | SCV002508527 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7; Autosomal recessive limb-girdle muscular dystrophy type 2U | 2021-05-07 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ISPD-related conditions. ClinVar contains an entry for this variant (Variation ID: 593707). This variant is present in population databases (rs778786691, ExAC 0.002%). This sequence change replaces glutamic acid with lysine at codon 239 of the ISPD protein (p.Glu239Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. |
Ambry Genetics | RCV004026955 | SCV004082449 | uncertain significance | not specified | 2023-07-12 | criteria provided, single submitter | clinical testing | The c.715G>A (p.E239K) alteration is located in exon 4 (coding exon 4) of the ISPD gene. This alteration results from a G to A substitution at nucleotide position 715, causing the glutamic acid (E) at amino acid position 239 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Gene |
RCV000728823 | SCV005376430 | uncertain significance | not provided | 2023-11-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26687144) |