Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001573800 | SCV005736978 | uncertain significance | not provided | 2025-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 279 of the IHH protein (p.Thr279Met). This variant is present in population databases (rs776499803, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with IHH-related conditions. ClinVar contains an entry for this variant (Variation ID: 1206307). 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 IHH 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. |
Laboratory of Diagnostic Genome Analysis, |
RCV001573800 | SCV001800182 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001573800 | SCV001972581 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Prevention |
RCV004746432 | SCV005354479 | uncertain significance | IHH-related disorder | 2024-03-13 | no assertion criteria provided | clinical testing | The IHH c.836C>T variant is predicted to result in the amino acid substitution p.Thr279Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.015% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |