ClinVar Miner

Submissions for variant NM_000304.4(PMP22):c.199G>C (p.Ala67Pro) (rs104894623)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000992662 SCV001145109 likely pathogenic not provided 2019-04-30 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/282556 chr). Predicted to have a damaging effect on the protein. Statistically associated with disease, but in a single family (p < 0.05).
Invitae RCV001047019 SCV001210949 pathogenic Charcot-Marie-Tooth disease, type I 2019-10-03 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 67 of the PMP22 protein (p.Ala67Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Charcot-Marie-Tooth disease and deafness in a family (PMID: 10330345, 11920834) and has been observed in unrelated individuals with Charcot-Marie-Tooth disease (Invitae). This variant is also known as 248G>C in the literature. ClinVar contains an entry for this variant (Variation ID: 8436). 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. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008951 SCV000029161 pathogenic Charcot-Marie-Tooth disease and deafness 1999-06-01 no assertion criteria provided literature only
GeneReviews RCV000008951 SCV000055664 pathologic Charcot-Marie-Tooth disease and deafness 2012-10-18 no assertion criteria provided curation Converted during submission to Pathogenic.

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