ClinVar Miner

Submissions for variant NM_000027.4(AGA):c.436T>G (p.Leu146Val) (rs146381591)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489452 SCV000577683 likely pathogenic not provided 2015-07-18 criteria provided, single submitter clinical testing The L146V variant in the AGA gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Sequencing Project reports the L146V variant was observed in 13/8600 alleles (0.15%) and 23/4406 alleles (0.52%) from individuals of European and African background respectively, indicating it may be a rare variant in these populations; no individuals within these control groups were reported as homozygous for this variant. The L146V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (F135S and S147P) have been reported in the Human Gene Mutation Database in the homozygous state association with aspartylglucosaminuria (Stenson et al., 2014), supporting the functional importance of this region of the protein. The L146V variant is a strong candidate for a disease-causing variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000634564 SCV000755894 likely benign Aspartylglucosaminuria 2020-12-04 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000634564 SCV000782733 uncertain significance Aspartylglucosaminuria 2017-09-21 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000489452 SCV000856364 uncertain significance not provided 2017-08-29 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000634564 SCV000930199 uncertain significance Aspartylglucosaminuria 2019-04-27 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000634564 SCV001306083 uncertain significance Aspartylglucosaminuria 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Institute of Human Genetics, University of Leipzig Medical Center RCV000634564 SCV001429165 uncertain significance Aspartylglucosaminuria 2016-12-16 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV000634564 SCV001623489 uncertain significance Aspartylglucosaminuria 2021-05-18 criteria provided, single submitter clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001251883 SCV001427629 uncertain significance Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

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