Submissions for variant NM_019066.5(MAGEL2):c.539T>C (p.Val180Ala)

gnomAD frequency: 0.00014  dbSNP: rs58729661

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV002540746	SCV002011537	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002540746	SCV003025169	uncertain significance	not provided	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 180 of the MAGEL2 protein (p.Val180Ala). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1319713). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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	RCV002540745	SCV003689809	likely benign	Inborn genetic diseases	2022-06-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity	RCV001771694	SCV003815364	uncertain significance	Schaaf-Yang syndrome	2019-09-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002540746	SCV004131411	benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	MAGEL2: BS1, BS2