Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001314538 | SCV001505074 | uncertain significance | Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 238 of the SLC26A2 protein (p.Phe238Val). This variant is present in population databases (rs746734591, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC26A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1015650). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC26A2 protein function. 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, |
RCV001810723 | SCV002050249 | uncertain significance | not provided | 2021-07-16 | criteria provided, single submitter | clinical testing | The SLC26A2 c.712T>G; p.Phe238Val variant (rs746734591), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is reported in ClinVar (Variation ID: 1015650) and is only observed on five alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The phenylalanine at codon 238 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.288). Due to limited information, the clinical significance of this variant is uncertain at this time. |
Natera, |
RCV001830283 | SCV002081850 | uncertain significance | Achondrogenesis, type IB | 2020-05-14 | no assertion criteria provided | clinical testing |