Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001959010 | SCV002243264 | pathogenic | Trichorhinophalangeal syndrome, type III; Trichorhinophalangeal dysplasia type I | 2020-12-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with trichorhinophalangeal syndrome (PMID: 23621477). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg257*) in the TRPS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRPS1 are known to be pathogenic (PMID: 11112658). |
| Victorian Clinical Genetics Services, |
RCV002471204 | SCV002766941 | pathogenic | Trichorhinophalangeal dysplasia type I | 2022-09-02 | 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 trichorhinophalangeal syndrome, type I (MIM#190350). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic by a clinical laboratory in ClinVar and observed as de novo in an individual with trichorhinophalangeal syndrome type I (PMID: 23621477). (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) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV003314028 | SCV004013432 | pathogenic | TRPS1-related disorder | 2023-04-25 | criteria provided, single submitter | clinical testing | PVS1, PS4_Supporting, PM2, PM6 |
| Genetics and Molecular Pathology, |
RCV002471204 | SCV004175242 | pathogenic | Trichorhinophalangeal dysplasia type I | 2023-05-16 | criteria provided, single submitter | clinical testing | The TRPS1 c.769C>T variant is classified as a PATHOGENIC variant (PVS1, PS4_moderate, PM2, PP4) The variant is a single nucleotide change at exon 3/7 of the TRPS1 gene which is predicted to result in a premature termination of the protein product at codon 257. This variant is predicted to cause loss of normal protein function which is a known mechanism of disease for the TRPS1 gene (PVS1). The variant has not been reported in dbSNP and is absent from population databases (PM2). The variant has been previously identified in at least two (or more) individuals affected with Trichorhinoplalangeal syndrome (PMID: 23621477, ClinVar) (PS4_moderate). The variant has been reported in ClinVar (Variation ID: #1459463) or HGMD (Accession no.: CM134356) as Pathogenic/ disease causing. The patient's phenotype is highly specific for the TRPS1 gene (PP4). |
| Zotz- |
RCV002471204 | SCV003916021 | likely pathogenic | Trichorhinophalangeal dysplasia type I | 2023-04-13 | no assertion criteria provided | clinical testing |