Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001901605 | SCV002173333 | uncertain significance | Combined immunodeficiency due to STK4 deficiency | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with arginine at codon 238 of the STK4 protein (p.Thr238Arg). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is present in population databases (rs750661803, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with STK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1404358). 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 STK4 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ambry Genetics | RCV003167088 | SCV003877586 | uncertain significance | Inborn genetic diseases | 2023-03-06 | criteria provided, single submitter | clinical testing | The c.713C>G (p.T238R) alteration is located in exon 7 (coding exon 7) of the STK4 gene. This alteration results from a C to G substitution at nucleotide position 713, causing the threonine (T) at amino acid position 238 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |