Submissions for variant NM_021076.4(NEFH):c.1095del (p.Gln365fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470530	SCV002768672	uncertain significance	Charcot-Marie-Tooth disease axonal type 2CC	2020-07-02	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3B-VUS. Following criteria are met: 0101 - Gain-of-function is a known mechanism of disease for this gene. Type 2CC axonal Charcot-Marie-Tooth disease has been associated with variants causing frameshift and elongation of NEFH protein, resulting in abnormal protein aggregation (PMID: 30992180). (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 3 of 4). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0704 - Comparable variant has low previous evidence for pathogenicity. An NMD-predicted variant has been reported as likely pathogenic but without clear evidence (ClinVar). (P) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign