Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001983042 | SCV002244584 | pathogenic | Familial meningioma | 2021-11-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SMARCE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu110*) in the SMARCE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMARCE1 are known to be pathogenic (PMID: 23377182). |
| Ambry Genetics | RCV002324410 | SCV002606040 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-13 | criteria provided, single submitter | clinical testing | The p.E110* pathogenic mutation (also known as c.328G>T), located in coding exon 5 of the SMARCE1 gene, results from a G to T substitution at nucleotide position 328. This changes the amino acid from a glutamic acid to a stop codon within coding exon 5. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Loss-of-function variants in SMARCE1 are known to cause increased risk of meningiomas; however, such associations with neurodevelopmental disorders are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Smith JM et al. Nat Genet. 2013 Mar;45(3):295-8). Based on the supporting evidence, this alteration is pathogenic for an increased risk of meningiomas; however, the association of this alteration with an increased risk of Coffin-Siris syndrome is unlikely. |