Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003232188 | SCV001205799 | pathogenic | Sotos syndrome | 2021-08-27 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV003232188 | SCV002557124 | pathogenic | Sotos syndrome | 2023-07-16 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Sotos syndrome (MIM#117550). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from histidine to arginine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0601 - Variant is located in the well-established functional consensus zinc binding motif within the PHD domain (NCBI conserved domains, PMID: 12464997). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. This alternative change (p.(His1616Leu)) has been reported as de novo in a single individual with childhood overgrowth and intellectual disability (PMID: 28475857, PMID: 12464997). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic and observed in at least two individuals with overgrowth syndrome. In one of these individuals, the variant was de novo (ClinVar, PMID: 28475857). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1102 - Strong phenotype match for this individual. (SP) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed) (by segregation analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Ce |
RCV004597951 | SCV005092625 | pathogenic | not provided | 2024-07-01 | criteria provided, single submitter | clinical testing | NSD1: PM1, PM2, PM5, PP4:Moderate, PP3, PS4:Supporting |