ClinVar Miner

Submissions for variant NM_031443.4(CCM2):c.1091A>G (p.His364Arg)

gnomAD frequency: 0.00005  dbSNP: rs201559289
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001955131 SCV002212111 uncertain significance Cerebral cavernous malformation 2 2023-08-30 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 364 of the CCM2 protein (p.His364Arg). This variant is present in population databases (rs201559289, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CCM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1434843). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CCM2 protein function. 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 RCV002442903 SCV002734892 likely benign Inborn genetic diseases 2021-08-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV003225207 SCV003921615 uncertain significance not provided 2022-10-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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