Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001354362 | SCV001548959 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | The SYNE1 p.Gln802* variant was not identified in the literature nor was it identified in dbSNP, ClinVar, LOVD 3.0 or in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (March 6, 2019, v2.1.1). The c.2404C>T variant leads to a premature stop codon at position 802 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the SYNE1 gene are an established mechanism of disease in SYNE1 deficiency and is the type of variant expected to cause the disorder in the homozygous or compound heterozygous state. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. |