Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000658128 | SCV000779899 | uncertain significance | not provided | 2018-05-17 | criteria provided, single submitter | clinical testing | The H21R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H21R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, the H21R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV000809882 | SCV000950063 | uncertain significance | Jeune thoracic dystrophy; Nephronophthisis | 2025-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 21 of the TTC21B protein (p.His21Arg). This variant is present in population databases (rs757283243, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TTC21B-related conditions. ClinVar contains an entry for this variant (Variation ID: 546277). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TTC21B protein function with a negative predictive value of 80%. 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. |
| ARUP Laboratories, |
RCV001002060 | SCV001159891 | uncertain significance | not specified | 2018-09-04 | criteria provided, single submitter | clinical testing | The TTC21B c.62A>G; p.His21Arg variant (rs757283243), to our knowledge, is not described in the medical literature but contains an entry in ClinVar (Variation ID: 546277). It is observed in the general population at an overall frequency of 0.0022% (6/273482 alleles) in the Genome Aggregation Database. The histidine at codon 21 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. However, due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty. |
| Fulgent Genetics, |
RCV002493070 | SCV002785822 | uncertain significance | Asphyxiating thoracic dystrophy 4; Nephronophthisis 12 | 2021-09-20 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004026022 | SCV004972699 | uncertain significance | Inborn genetic diseases | 2024-01-16 | criteria provided, single submitter | clinical testing | The c.62A>G (p.H21R) alteration is located in exon 2 (coding exon 2) of the TTC21B gene. This alteration results from a A to G substitution at nucleotide position 62, causing the histidine (H) at amino acid position 21 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |