Submissions for variant NM_006158.4(NEFL):c.1175T>A (p.Leu392His) (rs1554497393)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000640658	SCV000762253	uncertain significance	Charcot-Marie-Tooth disease type 2E	2019-07-23	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with histidine at codon 392 of the NEFL protein (p.Leu392His). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Charcot-Marie-Tooth disease and has also been observed to segregate with disease in a family (Invitae). ClinVar contains an entry for this variant (Variation ID: 533509). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV001090303	SCV001245756	uncertain significance	not provided	2019-07-01	criteria provided, single submitter	clinical testing