Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002457297 | SCV002613943 | uncertain significance | Cardiovascular phenotype | 2021-12-14 | criteria provided, single submitter | clinical testing | The p.R1158* variant (also known as c.3472C>T), located in coding exon 22 of the SOS1 gene, results from a C to T substitution at nucleotide position 3472. This changes the amino acid from an arginine to a stop codon within coding exon 22. This alteration occurs at the 3' terminus of theSOS1 gene, is not expected to trigger nonsense-mediated mRNAdecay, and impacts the last 176 amino acids of the protein. The exact functional effect of this alteration is unknown. Additionally, loss of function of SOS1 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV003236925 | SCV003935627 | uncertain significance | not provided | 2024-12-26 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation as the last 176 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29493581) |
Labcorp Genetics |
RCV003775636 | SCV004642744 | uncertain significance | RASopathy | 2023-08-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1158*) in the SOS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 176 amino acid(s) of the SOS1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1731751). 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. |