ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.736A>G (p.Lys246Glu) (rs119450944)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000002570 SCV000631370 likely pathogenic Adenylosuccinate lyase deficiency 2017-01-27 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 246 of the ADSL protein (p.Lys246Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the compound heterozygous state in 3 individuals affected with adenylosuccinate lyase deficiency (PMID: 10090474, 27504266). In 2 of these individuals laboratory testing detected elevated urine succinylpurine levels, findings that are characteristic for adenylosuccinate lyase deficiency (PMID: 1405483, 10090474, 27504266). ClinVar contains an entry for this variant (Variation ID: 2466). Experimental studies have shown that this missense change prevents ADSL homotetramer formation and leads to reduced ADSL enzyme activity (PMID: 19405474). In summary, this variant is a rare missense change that has been reported in affected individuals and has been found to impact protein function in vitro. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000002570 SCV000022728 pathogenic Adenylosuccinate lyase deficiency 1999-01-01 no assertion criteria provided literature only

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