ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.71A>G (p.Tyr24Cys) (rs539994406)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000529284 SCV000629208 uncertain significance Phenylketonuria 2018-01-17 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 24 of the PAH protein (p.Tyr24Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs539994406, ExAC 0.1%) but has not been reported in the literature in individuals with a PAH-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV000529284 SCV001266461 uncertain significance Phenylketonuria 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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