Submissions for variant NM_203447.4(DOCK8):c.221G>T (p.Ser74Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003761616	SCV003785846	uncertain significance	Autosomal recessive hyper-IgE syndrome	2022-09-27	criteria provided, single submitter	clinical testing	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. 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 DOCK8 protein function. This variant has not been reported in the literature in individuals affected with DOCK8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 74 of the DOCK8 protein (p.Ser74Ile).
Ambry Genetics	RCV004621754	SCV005113994	uncertain significance	Inborn genetic diseases	2024-03-25	criteria provided, single submitter	clinical testing	The c.221G>T (p.S74I) alteration is located in exon 3 (coding exon 3) of the DOCK8 gene. This alteration results from a G to T substitution at nucleotide position 221, causing the serine (S) at amino acid position 74 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.