Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000704305 | SCV000833249 | uncertain significance | not provided | 2022-05-31 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 264 of the SMARCB1 protein (p.Ile264Val). This variant has not been reported in the literature in individuals affected with SMARCB1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 580688). |
Ambry Genetics | RCV002422590 | SCV002676929 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-25 | criteria provided, single submitter | clinical testing | The p.I264V variant (also known as c.790A>G), located in coding exon 6 of the SMARCB1 gene, results from an A to G substitution at nucleotide position 790. The isoleucine at codon 264 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Missense and in-frame variants in SMARCB1 are known to cause neurodevelopmental disorders; however, such associations with rhabdoid tumor predisposition syndrome are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Eaton KW et al. Pediatr Blood Cancer. 2011 Jan;56(1):7-15). Based on the supporting evidence, the association of this alteration with Coffin-Siris syndrome is unknown; however, the association of this alteration with SMARCB1-related tumor predisposition syndrome is unlikely. |
Fulgent Genetics, |
RCV005027875 | SCV005660983 | uncertain significance | SMARCB1-related schwannomatosis; Rhabdoid tumor predisposition syndrome 1; Intellectual disability, autosomal dominant 15 | 2024-03-22 | criteria provided, single submitter | clinical testing |