Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000038915 | SCV000062593 | likely benign | not specified | 2015-05-20 | criteria provided, single submitter | clinical testing | p.His440Tyr in exon 12 of PRKAG2: This variant is not expected to have clinical significance due to its frequency in the general population and lack of evolutio nary conservation of the affected amino acid. It has been identified in 0.2% (20 /10406) of African chromosomes by the Exome Aggregation Consortium (ExAC, http:/ /exac.broadinstitute.org; dbSNP rs201878539) and 3 mammals (guinea pig, rabbit, and aardvark) have a tyrosine (Tyr) at this position despite high nearby amino a cid conservation, suggesting that this change may be tolerated. |
Gene |
RCV000038915 | SCV000208954 | likely benign | not specified | 2017-12-15 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Eurofins Ntd Llc |
RCV000724478 | SCV000225670 | uncertain significance | not provided | 2014-12-29 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001081726 | SCV000561815 | likely benign | Lethal congenital glycogen storage disease of heart | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000621627 | SCV000740112 | likely benign | Cardiovascular phenotype | 2019-03-13 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Color Diagnostics, |
RCV001178107 | SCV001342463 | likely benign | Cardiomyopathy | 2018-12-06 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000038915 | SCV001363080 | likely benign | not specified | 2019-11-11 | criteria provided, single submitter | clinical testing | Variant summary: PRKAG2 c.1318C>T (p.His440Tyr) results in a conservative amino acid change located in the CBS domain (IPR000644) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 282880 control chromosomes, predominantly at a frequency of 0.0017 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 68 fold the estimated maximal expected allele frequency for a pathogenic variant in PRKAG2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1318C>T has been reported in the literature in an individual affected with dilated Cardiomyopathy (Pugh_2014). This report however, does not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as likely benign (n=3) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
ARUP Laboratories, |
RCV000724478 | SCV002047746 | likely benign | not provided | 2021-11-09 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003904932 | SCV004721343 | likely benign | PRKAG2-related condition | 2022-01-27 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |