Submissions for variant NM_000528.4(MAN2B1):c.2992C>T (p.Arg998Cys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003067309	SCV003453704	uncertain significance	Deficiency of alpha-mannosidase	2022-08-16	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 998 of the MAN2B1 protein (p.Arg998Cys). This variant is present in population databases (rs758755293, 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Laboratory of Prof. Karen Avraham, Tel Aviv University	RCV003067309	SCV005073761	likely pathogenic	Deficiency of alpha-mannosidase	2024-05-29	criteria provided, single submitter	research	Homozygosity of a rare variant that is predicted to cause damage by most prediction programs