Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000571667 | SCV000672158 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | The p.S78Y variant (also known as c.233C>A), located in coding exon 2 of the SMARCA4 gene, results from a C to A substitution at nucleotide position 233. The serine at codon 78 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Missense and in-frame variants in SMARCA4 are known to cause neurodevelopmental disorders; however, such associations with rhabdoid tumor predisposition syndrome including small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Jelinic P et al. Nat Genet. 2014 May;46(5):424-6). Based on the supporting evidence, the association of this alteration with Coffin-Siris syndrome is unknown; however, the association of this alteration with rhabdoid tumor predisposition syndrome is unlikely. |
| Labcorp Genetics |
RCV001858347 | SCV002200761 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2022-07-19 | criteria provided, single submitter | clinical testing | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). ClinVar contains an entry for this variant (Variation ID: 484883). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 78 of the SMARCA4 protein (p.Ser78Tyr). |
| Baylor Genetics | RCV001858347 | SCV005052754 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2024-02-08 | criteria provided, single submitter | clinical testing |