Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000545724 | SCV000639936 | uncertain significance | Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 400 of the SYN1 protein (p.Asp400Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with SYN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 465087). 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: "Possibly 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. |
| Ambry Genetics | RCV003380610 | SCV004090471 | uncertain significance | Inborn genetic diseases | 2023-09-14 | criteria provided, single submitter | clinical testing | The c.1198G>A (p.D400N) alteration is located in exon 10 (coding exon 10) of the SYN1 gene. This alteration results from a G to A substitution at nucleotide position 1198, causing the aspartic acid (D) at amino acid position 400 to be replaced by an asparagine (N). Based on data from gnomAD, the A allele has an overall frequency of 0.001% (1/172896) total alleles studied. The highest observed frequency was 0.001% (1/76682) of European (non-Finnish) alleles. This amino acid position is not well conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |