ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.548T>A (p.Leu183His) (rs185797496)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000590199 SCV000697171 likely benign not specified 2019-04-02 criteria provided, single submitter clinical testing Variant summary: HEXA c.548T>A (p.Leu183His) results in a non-conservative amino acid change located in the Glycoside hydrolase family 20, catalytic domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00038 in 276944 control chromosomes, predominantly at a frequency of 0.0053 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in HEXA causing Tay-Sachs Disease phenotype (0.0014), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.548T>A in individuals affected with Tay-Sachs Disease and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Counsyl RCV000670879 SCV000795792 likely benign Tay-Sachs disease 2017-11-17 criteria provided, single submitter clinical testing
Invitae RCV000860726 SCV001000863 likely benign not provided 2019-02-21 criteria provided, single submitter clinical testing

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