Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001389726 | SCV001591179 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2024-08-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1653*) in the SMARCA4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acid(s) of the SMARCA4 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neuroblastoma (PMID: 31018240). ClinVar contains an entry for this variant (Variation ID: 1075995). 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. |
Ambry Genetics | RCV002341833 | SCV002643933 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-30 | criteria provided, single submitter | clinical testing | The p.R1653* variant (also known as c.4957C>T), located in coding exon 34 of the SMARCA4 gene, results from a C to T substitution at nucleotide position 4957. This changes the amino acid from an arginine to a stop codon within coding exon 34. Premature stop codons are typically deleterious in nature, however, this stop codon occurs at the 3' terminus of SMARCA4 , is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 27 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |