Submissions for variant NM_004637.5(RAB7A):c.167T>C (p.Leu56Pro) (rs775104487)

Minimum review status:		Collection method:
Minimum conflict level:
		ClinVar version:

Total submissions: 2

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235278	SCV000293055	uncertain significance	not provided	2017-04-06	criteria provided, single submitter	clinical testing	The L56P variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L56P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not highly conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV000698626	SCV000827304	uncertain significance	Charcot-Marie-Tooth disease, axonal, type 2b	2018-02-14	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with proline at codon 56 of the RAB7A protein (p.Leu56Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs775104487, ExAC 0.01%). This variant has not been reported in the literature in individuals with RAB7A-related disease. ClinVar contains an entry for this variant (Variation ID: 245880). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.