ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1278T>C (p.Asn426=) (rs59326968)

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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 RCV000400696 SCV000852128 benign Phenylketonuria 2018-08-10 reviewed by expert panel curation PAH-specific ACMG/AMP criteria applied: BA1: MAF=0.16641; BP4: no impact on gene in SIFT, Polyphen2, MutationTaster. In summary this variant meets criteria to be classified as benign for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (BA1, BP4).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078509 SCV000110365 benign not specified 2012-10-18 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000078509 SCV000303442 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000400696 SCV000375559 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000078509 SCV000601709 benign not specified 2016-10-13 criteria provided, single submitter clinical testing
Invitae RCV000400696 SCV000629178 benign Phenylketonuria 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000088823 SCV000696435 benign not provided 2017-07-31 criteria provided, single submitter clinical testing Variant summary: The PAH c.1278T>C (p.Asn426Asn) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may alter ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1666/121610 control chromosomes (104 homozygotes), predominantly in the African cohort at a frequency of 0.14655 (1525/10406). This frequency is about 19 times the estimated maximal expected allele frequency of a pathogenic PAH variant (0.0079057), suggesting this is likely a benign polymorphism found primarily in population(s) of African origin. A publication, Acosta_2001, classifies the variant as a polymorphism, along with multiple clinical diagnostic laboratories classify the variant as "likely benign/benign." Taken together, this variant is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000088823 SCV000888342 benign not provided 2016-10-13 criteria provided, single submitter clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088823 SCV000119414 not provided not provided no assertion provided not provided

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