ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.748G>A (p.Gly250Ser) (rs1057521137)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000443171 SCV000521180 pathogenic not provided 2018-05-15 criteria provided, single submitter clinical testing The G250S missense variant has been reported in multiple French Canadian individuals from Quebec who were biochemically confirmed to be carriers of Tay-Sachs disease (Triggs-Raine et al. 1995). Expression of G250S in COS-7 cells found that this variant is associated with approximately 4% residual beta-hexosaminidase activity (Martin et al. 2007). G250S was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G250S variant is a non-conservative amino acid substitution, it occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, a missense change at the same position (G250D) has also been reported in association with Tay-Sachs disease (Trop et al. 1992). In summary, we interpret G250S to be a pathogenic variant.
Counsyl RCV000675102 SCV000800638 uncertain significance Tay-Sachs disease 2017-12-14 criteria provided, single submitter clinical testing

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