ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.439A>G (p.Thr147Ala)

gnomAD frequency: 0.00003  dbSNP: rs371437767
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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 RCV000546803 SCV000644829 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2023-03-07 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 468276). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 147 of the DCTN1 protein (p.Thr147Ala).
GeneDx RCV001755849 SCV002005007 uncertain significance not provided 2021-03-16 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003278899 SCV003962464 uncertain significance Inborn genetic diseases 2023-05-17 criteria provided, single submitter clinical testing The c.439A>G (p.T147A) alteration is located in exon 7 (coding exon 7) of the DCTN1 gene. This alteration results from a A to G substitution at nucleotide position 439, causing the threonine (T) at amino acid position 147 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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