Submissions for variant NM_000642.3(AGL):c.341G>A (p.Arg114His)

gnomAD frequency: 0.00011  dbSNP: rs150146360

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000699069	SCV000827764	uncertain significance	Glycogen storage disease type III	2022-07-19	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 114 of the AGL protein (p.Arg114His). This variant is present in population databases (rs150146360, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with AGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 576547). 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 histidine 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	RCV002534368	SCV003758928	uncertain significance	Inborn genetic diseases	2022-10-27	criteria provided, single submitter	clinical testing	The c.341G>A (p.R114H) alteration is located in exon 4 (coding exon 3) of the AGL gene. This alteration results from a G to A substitution at nucleotide position 341, causing the arginine (R) at amino acid position 114 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV003151807	SCV003840387	uncertain significance	not provided	2022-09-12	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003330911	SCV004038408	uncertain significance	not specified	2023-08-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000699069	SCV004049919	uncertain significance	Glycogen storage disease type III	2023-04-11	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000699069	SCV002091442	uncertain significance	Glycogen storage disease type III	2019-10-28	no assertion criteria provided	clinical testing