Submissions for variant NM_012448.4(STAT5B):c.676C>T (p.Arg226Cys)

gnomAD frequency: 0.00001  dbSNP: rs777110652

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001351627	SCV001546117	uncertain significance	Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	2021-04-10	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with STAT5B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces arginine with cysteine at codon 226 of the STAT5B protein (p.Arg226Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine.
PreventionGenetics, part of Exact Sciences	RCV003393997	SCV004119788	uncertain significance	STAT5B-related disorder	2023-01-22	criteria provided, single submitter	clinical testing	The STAT5B c.676C>T variant is predicted to result in the amino acid substitution p.Arg226Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0030% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-40371735-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.