ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.212G>A (p.Gly71Glu)

dbSNP: rs67586389
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001531491 SCV001746658 pathogenic not provided 2024-01-01 criteria provided, single submitter clinical testing DCTN1: PP1:Strong, PM1, PM2, PM5, PS4:Moderate, PP3
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000020576 SCV002764665 pathogenic Perry syndrome 2020-09-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003764613 SCV004569188 pathogenic Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2023-06-15 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 DCTN1 protein function. ClinVar contains an entry for this variant (Variation ID: 21390). This missense change has been observed in individuals with Perry syndrome (PMID: 19136952, 24343258, 28625595, 32717578). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 71 of the DCTN1 protein (p.Gly71Glu).
Genomic Diagnostics Laboratory, National Institute of Medical Genomics RCV000020576 SCV005039000 pathogenic Perry syndrome 2024-05-02 criteria provided, single submitter clinical testing Gly71Glu variant in DCTN1 has been reported previously in individuals with Perry síndrome (PMID: 19136952, 24343258, 28625595, 32717578). This variant is absent in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 71 of the DCTN1 protein (p.Gly71Glu). Acording to Farrer et al, 2009 (PMID: 19136952) functional analysis on a similar variant, Gly71Arg, revealed a modest decrease in microtubule binding comparable to Gly59Ser. We perfomed an in silico analyisis of this variant: Glu71 modifies the electrostatic potential of the CAP-Gly domain. Using ACMG Guidelines 2015, this is a pathogenic variant.
OMIM RCV000020576 SCV000187718 pathogenic Perry syndrome 2014-02-01 no assertion criteria provided literature only
Inherited Neuropathy Consortium Ii, University Of Miami RCV000020576 SCV004174366 uncertain significance Perry syndrome 2016-01-06 no assertion criteria provided literature only

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