Submissions for variant NM_000530.8(MPZ):c.234G>A (p.Ser78=)

dbSNP: rs368149365

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001231540	SCV001404066	uncertain significance	Charcot-Marie-Tooth disease, type I	2023-06-30	criteria provided, single submitter	clinical testing	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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. This sequence change affects codon 78 of the MPZ mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MPZ protein. This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon. This variant is present in population databases (rs368149365, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with MPZ-related conditions. ClinVar contains an entry for this variant (Variation ID: 958383).
Baylor Genetics	RCV001329968	SCV001521543	uncertain significance	Dejerine-Sottas disease	2020-02-07	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics	RCV002447158	SCV002732669	likely benign	Inborn genetic diseases	2020-11-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Uffe Birk Jensen Lab, Aarhus University Hospital	RCV003482910	SCV004012844	uncertain significance	Charcot-Marie-Tooth disease type 1B	2023-07-10	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003482910	SCV004804704	uncertain significance	Charcot-Marie-Tooth disease type 1B	2024-03-17	criteria provided, single submitter	research