Submissions for variant NM_019066.5(MAGEL2):c.1742A>C (p.His581Pro)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002632673	SCV003505061	uncertain significance	not provided	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 581 of the MAGEL2 protein (p.His581Pro). This variant is present in population databases (rs751478832, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with MAGEL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2186139). 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 MAGEL2 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.
Ambry Genetics	RCV002620040	SCV003725643	uncertain significance	Inborn genetic diseases	2022-07-11	criteria provided, single submitter	clinical testing	The c.1742A>C (p.H581P) alteration is located in exon 1 (coding exon 1) of the MAGEL2 gene. This alteration results from a A to C substitution at nucleotide position 1742, causing the histidine (H) at amino acid position 581 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV003134667	SCV003815374	uncertain significance	Schaaf-Yang syndrome	2020-07-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003936598	SCV004754188	uncertain significance	MAGEL2-related disorder	2023-12-29	criteria provided, single submitter	clinical testing	The MAGEL2 c.1742A>C variant is predicted to result in the amino acid substitution p.His581Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0078% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.