ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.1339T>C (p.Ser447Pro)

gnomAD frequency: 0.00001  dbSNP: rs777821034
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186696 SCV000240262 pathogenic not provided 2021-04-14 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Missense variants in nearby residues reported in the Human Gene Mutation Database (Stenson et al., 2014); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29655203, 12016589, 16839792)
Fulgent Genetics, Fulgent Genetics RCV000763485 SCV000894270 pathogenic Adenylosuccinate lyase deficiency 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000763485 SCV001522758 pathogenic Adenylosuccinate lyase deficiency 2020-09-02 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV000763485 SCV002224008 likely pathogenic Adenylosuccinate lyase deficiency 2023-06-26 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 ADSL protein function. ClinVar contains an entry for this variant (Variation ID: 204801). This missense change has been observed in individual(s) with adenylosuccinate lyase deficiency (PMID: 12016589). This variant is present in population databases (rs777821034, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 447 of the ADSL protein (p.Ser447Pro).
Revvity Omics, Revvity RCV000763485 SCV003820488 uncertain significance Adenylosuccinate lyase deficiency 2023-08-01 criteria provided, single submitter clinical testing

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