Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000005333 | SCV001411255 | pathogenic | Giant axonal neuropathy 1 | 2023-06-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 5030). This missense change has been observed in individual(s) with giant axonal neuropathy (PMID: 11062483, 20949505). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs119485088, gnomAD 0.004%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 486 of the GAN protein (p.Glu486Lys). |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000005333 | SCV002512623 | likely pathogenic | Giant axonal neuropathy 1 | 2022-02-03 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4 moderate, PM2 moderate, PM3 strong, BP4 supporting |
Ambry Genetics | RCV002390092 | SCV002695893 | likely pathogenic | Inborn genetic diseases | 2019-12-19 | criteria provided, single submitter | clinical testing | The p.E486K variant (also known as c.1456G>A), located in coding exon 9 of the GAN gene, results from a G to A substitution at nucleotide position 1456. The glutamic acid at codon 486 is replaced by lysine, an amino acid with similar properties. This variant was homozygous in a Tunisian family and compound heterozygous with a nonsense variant in a French family with giant axonal neuropathy (GAN) (Bomont P et al. Nat. Genet., 2000 Nov;26:370-4). Another affected individual was found to carry this alteration in trans with a microdeletion involving exons 3-11 of the GAN gene (Mahammad S et al. J. Clin. Invest., 2013 May;123:1964-75). This variant was not reported in the ExAC database, with coverage at this position. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
3billion | RCV000005333 | SCV005906207 | likely pathogenic | Giant axonal neuropathy 1 | 2023-12-07 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.35 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.69 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000005030 /PMID: 11062483). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 11062483, 20949505). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
OMIM | RCV000005333 | SCV000025511 | pathogenic | Giant axonal neuropathy 1 | 2000-11-01 | no assertion criteria provided | literature only | |
Inherited Neuropathy Consortium Ii, |
RCV000005333 | SCV004174515 | uncertain significance | Giant axonal neuropathy 1 | 2016-01-06 | no assertion criteria provided | literature only |