ClinVar Miner

Submissions for variant NM_000049.3(ASPA):c.340G>T (p.Asp114Tyr) (rs1446467099)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671501 SCV000796483 likely pathogenic Spongy degeneration of central nervous system 2017-12-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001194237 SCV001363610 pathogenic Canavan Disease, Familial Form 2019-11-04 criteria provided, single submitter clinical testing Variant summary: ASPA c.340G>T (p.Asp114Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251056 control chromosomes. c.340G>T has been reported in the literature in multiple individuals from families affected with Canavan Disease (Olsen_2002). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported although a different amino acid change at the same codon (p.Asp114Glu) has been reported to abolish enzyme activity to 0.35% of controls demonstrating an importance of residue 114 for the structure/function of the ASPA protein (Kaul_1996). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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