Submissions for variant NM_015338.6(ASXL1):c.724A>G (p.Met242Val)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002750417	SCV003012386	uncertain significance	not provided	2023-11-21	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 242 of the ASXL1 protein (p.Met242Val). This variant is present in population databases (rs765190948, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ASXL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1972886). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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	RCV002750416	SCV003735525	likely benign	Inborn genetic diseases	2024-11-28	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.
CeGaT Center for Human Genetics Tuebingen	RCV002750417	SCV004152568	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	ASXL1: BS2