Submissions for variant NM_000530.8(MPZ):c.486del (p.Ile162fs) (rs1571818248)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Raymond Lab,University of Cambridge	RCV000850194	SCV000897731	likely pathogenic	Intellectual disability	2019-02-13	criteria provided, single submitter	research
Invitae	RCV001040610	SCV001204194	pathogenic	Charcot-Marie-Tooth disease, type I	2019-12-17	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the MPZ gene (p.Ile162Metfs*90). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 87 amino acids of the MPZ protein and extend the protein by an additional 2 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 25614874). ClinVar contains an entry for this variant (Variation ID: 625199). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the region of the MPZ protein between p.Arg98 and p.Ser233. This region has been determined to be associated with autosomal dominant MPZ-related conditions (PMID: 7688964, 15729519, 20461396), which suggests that variants that occur in this region are likely to be clinically significant. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium	RCV000790075	SCV000929465	pathogenic	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only