ClinVar Miner

Submissions for variant NM_000016.6(ACADM):c.928G>A (p.Gly310Arg)

gnomAD frequency: 0.00003  dbSNP: rs747268471
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000173613 SCV000268501 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000173613 SCV000754918 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2023-11-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 310 of the ACADM protein (p.Gly310Arg). This variant is present in population databases (rs747268471, gnomAD 0.004%). This missense change has been observed in individual(s) with MCAD deficiency (PMID: 11349232, 18241067, 20434380, 23509891). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 193539). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACADM protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000173613 SCV000918376 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-11-20 criteria provided, single submitter clinical testing Variant summary: The ACADM c.928G>A (p.Gly310Arg) variant involves the alteration of a highly conserved nucleotide. The variant is located within the conserved Acyl-CoA dehydrogenase/oxidase C-terminal domain (InterPro) and 5/5 in silico tools predict a damaging outcome for this variant. These predictions were confirmed by functional studies, where G310R was shown to be defective and unstable due to compromised folding (Andresen_ 2001). This variant was found in 6/275998 control chromosomes in gnomAD at a frequency of 0.000021, which does not exceed the estimated maximal expected allele frequency of a pathogenic ACADM variant (0.0054006). The variant was identified in several affected individuals with biochemical profiles suggestive of an intermediate MCAD phenotype (Andresen_ 2001, Smith_2010, Touw_2013, Nichols_2008). The variant has been reported with conflicting interpretations of pathogenicity (VUS/Pathogenic) by different clinical diagnostic laboratories/reputable databases. Taken together, this variant is classified as Likely Pathogenic.
Revvity Omics, Revvity RCV000173613 SCV002023975 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2020-05-18 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000173613 SCV002060087 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2021-10-27 criteria provided, single submitter clinical testing NM_000016.4(ACADM):c.928G>A(G310R) is a missense variant classified as likely pathogenic in the context of medium chain acyl-CoA dehydrogenase deficiency. G310R has been observed in cases with relevant disease (PMID: 22630369, 20434380, 18241067, 27477829, 11349232). Functional assessments of this variant are available in the literature (PMID: 11349232). G310R has been observed in population frequency databases (gnomAD: AFR 0.01%). In summary, NM_000016.4(ACADM):c.928G>A(G310R) is a missense variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Baylor Genetics RCV000173613 SCV004212091 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2024-02-07 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000724339 SCV000224737 uncertain significance not provided 2014-10-31 flagged submission clinical testing
Undiagnosed Diseases Network, NIH RCV000173613 SCV004242221 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2020-04-30 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.