Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000509503 | SCV000227718 | uncertain significance | not provided | 2016-11-02 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000398651 | SCV000417621 | uncertain significance | Asphyxiating thoracic dystrophy 4 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV000304805 | SCV000417622 | uncertain significance | Nephronophthisis 12 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Invitae | RCV000634201 | SCV000755504 | likely benign | Jeune thoracic dystrophy; Nephronophthisis | 2024-01-24 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000509503 | SCV001157190 | uncertain significance | not provided | 2019-12-10 | criteria provided, single submitter | clinical testing | The TTC21B c.2587C>T; p.Arg863Trp variant (rs34489989) has been described in an individual who reportedly fulfilled diagnostic inclusion criteria for Bardet-Biedl syndrome (Redin 2012). It is reported as a variant of uncertain significance by multiple laboratories in ClinVar (Variation ID: 195531), and is observed in the general population at an overall frequency of 0.084% (237/282480 alleles), with increased frequency in the non-Finnish European population (0.17%) in the Genome Aggregation Database. The arginine at codon 863 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious to protein structure/function. However, due to limited information regarding this variant, its clinical significance cannot be determined with certainty. References: Redin C et al. Targeted high-throughput sequencing for diagnosis of genetically heterogeneous diseases: efficient mutation detection in Bardet-Biedl and Alström syndromes. J Med Genet 2012;9(8):502-512. |
Gene |
RCV000509503 | SCV001776469 | uncertain significance | not provided | 2020-12-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported previously in the heterozygous state in an individual with Bardet-Biedl syndrome; however, no second variant was identified (Redin et al., 2012); This variant is associated with the following publications: (PMID: 22773737) |
Victorian Clinical Genetics Services, |
RCV000398651 | SCV002768378 | uncertain significance | Asphyxiating thoracic dystrophy 4 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with nephronophthisis 12 (MIM#613820), short-rib thoracic dysplasia 4 with or without polydactyly (MIM#613819) and familial focal segmental glomerulosclerosis (FSGS). Partial loss of function has also been described, and associated with hypomorphic variants in this gene (OMIM, PMIDs: 24876116, 21258341). (I) 0106 - This gene is associated with autosomal recessive disease. Although OMIM refers to the association of this gene with autosomal dominant nephronophthisis 12 (MIM#613820), no specific evidence was found in the literature confirming this observation. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to tryptophan. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 237 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (p.R863Q: 11 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated TPR-repeat motif (UniProt). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been classified as a variant of uncertain significance by clinical diagnostic laboratories and is heterozygous in one individual with autosomal recessive Bardet-Biedl syndrome, with no classification provided (ClinVar, PMID: 22773737). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Revvity Omics, |
RCV000509503 | SCV003821649 | uncertain significance | not provided | 2020-02-19 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000509503 | SCV004147153 | uncertain significance | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | TTC21B: PM2 |
Prevention |
RCV004537393 | SCV004743635 | likely benign | TTC21B-related disorder | 2024-01-31 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Genome |
RCV000509503 | SCV000607229 | not provided | not provided | no assertion provided | phenotyping only | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. | |
Diagnostic Laboratory, |
RCV000509503 | SCV001742808 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000509503 | SCV001799234 | uncertain significance | not provided | no assertion criteria provided | clinical testing |