Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001037204 | SCV001200605 | uncertain significance | Glycogen storage disease due to muscle and heart glycogen synthase deficiency | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 222 of the GYS1 protein (p.Asn222Lys). This variant is present in population databases (rs201548356, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with GYS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 836150). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ambry Genetics | RCV002551376 | SCV003676099 | uncertain significance | Inborn genetic diseases | 2021-03-19 | criteria provided, single submitter | clinical testing | The c.666C>G (p.N222K) alteration is located in exon 4 (coding exon 4) of the GYS1 gene. This alteration results from a C to G substitution at nucleotide position 666, causing the asparagine (N) at amino acid position 222 to be replaced by a lysine (K). The p.N222K alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003413820 | SCV004107047 | uncertain significance | GYS1-related condition | 2023-10-04 | criteria provided, single submitter | clinical testing | The GYS1 c.666C>G variant is predicted to result in the amino acid substitution p.Asn222Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.072% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-49489119-G-C). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |