ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.735G>A (p.Val245=) (rs1042503)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000297921 SCV000852118 benign Phenylketonuria 2018-04-24 reviewed by expert panel curation The c.735G>A (p.Val245=) variant in PAH has a MAF of 0.29058 in ExAC (BA1; with 6,524 homozygotes (BS2). This is a synonymous variant, predicted tolerated and benign in SIFT, Polyphen. MutationTaster predicted polymorphism with no abrogation of splice sites (BP4). In summary, this variant meets criteria to be classified as benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078529 SCV000110385 benign not specified 2018-02-10 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000078529 SCV000303448 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000297921 SCV000375566 benign Phenylketonuria 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Integrated Genetics/Laboratory Corporation of America RCV000089066 SCV000696464 benign not provided 2016-04-05 criteria provided, single submitter clinical testing Variant summary: The variant of interest causes a synonymous change involving a non-conserved nucleotide with 3/5 Alamut algorithms predicting the creation of a splice donor site. However, these in silico predictions have not been confirmed with functional studies. This variant was found in 35308/121456 control chromosomes (6524 homozygotes) at a frequency of 0.2907061, which exceeds the predicted the maximal expected frequency of a pathogenic PAH allele (0.0079057), highly suggesting this variant is benign. In addition, a reputable clinical laboratory classifies the variant as Benign. The variant of interest is cited as a known common polymorphism in the literature. Taken together, this variant was classified as a Benign variant.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000297921 SCV000744095 benign Phenylketonuria 2014-10-10 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000089066 SCV000987626 benign not provided criteria provided, single submitter clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089066 SCV000119672 not provided not provided no assertion provided not provided
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000297921 SCV000733123 benign Phenylketonuria no assertion criteria provided clinical testing

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