ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.713G>A (p.Arg238His) (rs151319324)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000513790 SCV000610857 uncertain significance not provided 2017-08-23 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000513790 SCV000232517 uncertain significance not provided 2015-08-24 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000555818 SCV000896577 uncertain significance Carbohydrate-deficient glycoprotein syndrome type I 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000555818 SCV000633727 uncertain significance Carbohydrate-deficient glycoprotein syndrome type I 2018-01-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 238 of the PMM2 protein (p.Arg238His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs151319324, ExAC 0.1%) but has not been reported in the literature in individuals with a PMM2-related disease. ClinVar contains an entry for this variant (Variation ID: 198714). 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"). A different missense substitution at this codon (p.Arg238Pro) has been determined as likely pathogenic (PMID: 9497260, 10066032, 25681648). This suggests that the arginine residue is critical for PMM2 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is a rare missense change that affects an amino acid residue that is expected to be important for protein function. However, it is also found in the population at an appreciable frequency. For these reasons, it has been classified as a Variant of Uncertain Significance.

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