Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000726824 | SCV000618022 | uncertain significance | not provided | 2017-08-23 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the FKRP gene. The N424H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N424H variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The N424H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
EGL Genetic Diagnostics, |
RCV000726824 | SCV000703316 | uncertain significance | not provided | 2016-12-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000634052 | SCV000755330 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2019-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with histidine at codon 424 of the FKRP protein (p.Asn424His). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and histidine. This variant is present in population databases (rs769568971, ExAC 0.008%). This variant has not been reported in the literature in individuals with FKRP-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 C0"). 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. |
Centre for Mendelian Genomics, |
RCV001197776 | SCV001368555 | uncertain significance | Polymicrogyria; Abnormality of neuronal migration | 2018-10-24 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PS3,PS4,PM2,PM4. This variant was detected in heterozygous state. |