Submissions for variant NM_000528.4(MAN2B1):c.1787T>G (p.Ile596Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003073627	SCV003446885	uncertain significance	Deficiency of alpha-mannosidase	2022-05-17	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 596 of the MAN2B1 protein (p.Ile596Ser). This variant is present in population databases (rs769653813, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with MAN2B1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine 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.
CeGaT Center for Human Genetics Tuebingen	RCV004721106	SCV005331283	uncertain significance	not provided	2024-07-01	criteria provided, single submitter	clinical testing	MAN2B1: PM2, BP4