Submissions for variant NM_000530.8(MPZ):c.428C>T (p.Thr143Met) (rs750724650)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000638163	SCV000759649	uncertain significance	Charcot-Marie-Tooth disease, type I	2017-12-20	criteria provided, single submitter	clinical testing	This sequence change replaces threonine with methionine at codon 143 of the MPZ protein (p.Thr143Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs750724650, ExAC 0.03%). This variant has been reported in an individual affected with Charcot-Marie-Tooth disease (CMT) and has been reported to segregate with CMT in a single family (PMID: 20456450). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; 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.
Illumina Clinical Services Laboratory,Illumina	RCV001097625	SCV001253922	uncertain significance	Charcot-Marie-Tooth disease, demyelinating, type 1b	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina	RCV001097626	SCV001253923	uncertain significance	Congenital hypomyelinating neuropathy 2	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina	RCV001097627	SCV001253924	uncertain significance	Charcot-Marie-Tooth disease dominant intermediate d	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina	RCV001097628	SCV001253925	uncertain significance	Roussy-Lévy syndrome	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Inherited Neuropathy Consortium	RCV000790102	SCV000929492	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only