Submissions for variant NM_004082.5(DCTN1):c.2768C>T (p.Pro923Leu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002912930	SCV003247717	uncertain significance	Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B	2022-10-10	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. 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. 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. This variant is present in population databases (rs752851562, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 923 of the DCTN1 protein (p.Pro923Leu).
PreventionGenetics, part of Exact Sciences	RCV003403940	SCV004118751	uncertain significance	DCTN1-related disorder	2023-03-01	criteria provided, single submitter	clinical testing	The DCTN1 c.2768C>T variant is predicted to result in the amino acid substitution p.Pro923Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-74593138-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.