Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189661 | SCV000243307 | uncertain significance | not provided | 2014-02-06 | criteria provided, single submitter | clinical testing | The A648V missense change in the SYN1 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 4,600 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one uncharged, non-polar amino acid for another at a position that is not conserved across species. However, in silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. The possibility that A648V is a disease-associated mutation cannot be excluded, since mutations in SYN1 are inherited in an X-linked manner and heterozygous female carriers of SYN1 mutations may be unaffected (Garcia et al., 2004) The variant is found in EPILEPSY panel(s). |
Invitae | RCV000794382 | SCV000933787 | uncertain significance | Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 648 of the SYN1 protein (p.Ala648Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD 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: 207476). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |