ClinVar Miner

Submissions for variant NM_007289.4(MME):c.1265C>A (p.Ala422Asp)

gnomAD frequency: 0.00001  dbSNP: rs777476150
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002508208 SCV002817477 uncertain significance not provided 2022-06-23 criteria provided, single submitter clinical testing Reported in an individual and their father with peripheral neuropathy and Charcot-Marie-Tooth disease type 2 respectively (Auer-Grumbach et al., 2016); Published functional studies suggest p.(A422D) results in decreased protein activity (Auer-Grumbach et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34480178, 33144514, 27588448)
Labcorp Genetics (formerly Invitae), Labcorp RCV002508208 SCV003525676 uncertain significance not provided 2022-09-06 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 422 of the MME protein (p.Ala422Asp). This variant is present in population databases (rs777476150, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 27588448; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 265744). 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. 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.
OMIM RCV000255510 SCV000322712 risk factor Charcot-Marie-Tooth disease axonal type 2T 2016-10-06 no assertion criteria provided literature only

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