ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.632C>T (p.Pro211Leu)

gnomAD frequency: 0.00002  dbSNP: rs763427780
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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 RCV001050536 SCV001214651 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2024-06-11 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 211 of the DCTN1 protein (p.Pro211Leu). 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 missense change has been observed in individual(s) with amyotrophic lateral sclerosis (ALS) (PMID: 25299611). ClinVar contains an entry for this variant (Variation ID: 847069). 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 with a negative predictive value of 80%. 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.
Inherited Neuropathy Consortium Ii, University Of Miami RCV003447315 SCV004174763 uncertain significance Perry syndrome 2016-01-06 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV004746214 SCV005353958 uncertain significance DCTN1-related disorder 2024-07-12 no assertion criteria provided clinical testing The DCTN1 c.632C>T variant is predicted to result in the amino acid substitution p.Pro211Leu. In the literature, this variant is reported via an alternate transcript NM_001135041 as c.230C>T (p.Pro77Leu). This variant has been reported in an individual with amyotrophic lateral sclerosis (ALS) (Tables S2 and S7,Couthouis et al. 2014. PubMed ID: 25299611). This variant is reported in 0.0042% of alleles in individuals of European (Non-Finnish) 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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