ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.1103A>G (p.Lys368Arg)

gnomAD frequency: 0.00001  dbSNP: rs764291005
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670797 SCV000795696 uncertain significance Tay-Sachs disease 2017-11-16 criteria provided, single submitter clinical testing
Invitae RCV000670797 SCV003277474 uncertain significance Tay-Sachs disease 2018-04-12 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 368 of the HEXA protein (p.Lys368Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs764291005, ExAC 0.01%). This variant has not been reported in the literature in individuals with HEXA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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