Submissions for variant NM_001626.6(AKT2):c.641C>T (p.Ala214Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002958636	SCV003278834	uncertain significance	Type 2 diabetes mellitus; Hypoinsulinemic hypoglycemia and body hemihypertrophy	2022-10-17	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with AKT2-related conditions. This variant is present in population databases (rs758767505, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 214 of the AKT2 protein (p.Ala214Val).
PreventionGenetics, part of Exact Sciences	RCV003403977	SCV004106080	uncertain significance	AKT2-related disorder	2023-03-24	criteria provided, single submitter	clinical testing	The AKT2 c.641C>T variant is predicted to result in the amino acid substitution p.Ala214Val. This variant has been reported as a variant of uncertain significance in a cohort study of patients with dyslipidemias; however, no additional studies were done to assess its pathogenicity (Dron et al. 2020. PubMed ID: 32041611). This variant is reported in 0.0056% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-40744879-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.