ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.620C>G (p.Ser207Cys)

dbSNP: rs397517277
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038951 SCV000062629 uncertain significance not specified 2012-07-06 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ser207Cys varia nt in PRKAG2 has not been reported in the literature nor previously identified i n >1500 Caucasian probands tested by our laboratory. In addition, this variant h as not been identified in large and broad populations by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS). This low frequency is consistent with a disease causing role but insufficient to establish this with confidence. Computational analyses (biochemical amino acid properties, conservation, AlignG VGD, PolyPhen2, and SIFT) suggest that the Ser207Cys variant may not impact the protein, though this information is not predictive enough to rule out pathogenic ity. In addition, the variant is located outside the CBS domain of the PRKAG2 pr otein that contains all pathogenic PRKAG2 variants have been identified to date. Additional information is needed to fully assess the clinical significance of the Ser207Cys variant.
Illumina Laboratory Services, Illumina RCV000371199 SCV000467636 uncertain significance Lethal congenital glycogen storage disease of heart 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001795010 SCV000467637 uncertain significance Wolff-Parkinson-White pattern 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000331754 SCV000467638 uncertain significance Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000371199 SCV001214023 uncertain significance Lethal congenital glycogen storage disease of heart 2021-12-02 criteria provided, single submitter clinical testing 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. 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 PRKAG2 protein function. ClinVar contains an entry for this variant (Variation ID: 45729). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 27532257, 32746448). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 207 of the PRKAG2 protein (p.Ser207Cys).
Fulgent Genetics, Fulgent Genetics RCV002477108 SCV002779105 uncertain significance Lethal congenital glycogen storage disease of heart; Hypertrophic cardiomyopathy 6; Wolff-Parkinson-White pattern 2021-09-09 criteria provided, single submitter clinical testing

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