Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000996907 | SCV001151898 | likely benign | not provided | 2017-08-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001368832 | SCV001565246 | uncertain significance | RYR1-Related Disorders | 2021-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 4463 of the RYR1 protein (p.Ala4463Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This missense change has been observed in individual(s) with autosomal dominant RYR1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 808568). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The valine 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. |