ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.1255G>A (p.Ala419Thr)

gnomAD frequency: 0.00002  dbSNP: rs922032527
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644465 SCV000766163 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2023-07-08 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 419 of the DCTN1 protein (p.Ala419Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with familial amyotrophic lateral sclerosis (PMID: 33408239). ClinVar contains an entry for this variant (Variation ID: 536150). 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 not expected to disrupt DCTN1 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 RCV002422329 SCV002680025 uncertain significance Inborn genetic diseases 2021-12-14 criteria provided, single submitter clinical testing The p.A419T variant (also known as c.1255G>A), located in coding exon 12 of the DCTN1 gene, results from a G to A substitution at nucleotide position 1255. The alanine at codon 419 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003918040 SCV004731216 uncertain significance DCTN1-related disorder 2024-02-08 criteria provided, single submitter clinical testing The DCTN1 c.1255G>A variant is predicted to result in the amino acid substitution p.Ala419Thr. This variant was reported in an individual with Amyotrophic lateral sclerosis (Corcia et al 2021. PubMed ID: 33408239). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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