ClinVar Miner

Submissions for variant NM_015164.4(PLEKHM2):c.3035G>A (p.Arg1012Gln)

gnomAD frequency: 0.00011  dbSNP: rs533946132
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000703947 SCV000832876 uncertain significance Dilated Cardiomyopathy, Recessive 2023-09-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1012 of the PLEKHM2 protein (p.Arg1012Gln). This variant is present in population databases (rs533946132, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PLEKHM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 580413). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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.
Ambry Genetics RCV002536377 SCV003683971 uncertain significance Inborn genetic diseases 2022-04-08 criteria provided, single submitter clinical testing The c.3035G>A (p.R1012Q) alteration is located in exon 20 (coding exon 20) of the PLEKHM2 gene. This alteration results from a G to A substitution at nucleotide position 3035, causing the arginine (R) at amino acid position 1012 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Preventiongenetics, part of Exact Sciences RCV003424298 SCV004117969 uncertain significance PLEKHM2-related condition 2023-07-18 criteria provided, single submitter clinical testing The PLEKHM2 c.3035G>A variant is predicted to result in the amino acid substitution p.Arg1012Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.010% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-16060404-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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