ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.409C>T (p.Arg137Ter) (rs121907962)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255817 SCV000322431 pathogenic not provided 2016-04-27 criteria provided, single submitter clinical testing The R137X pathogenic variant in the HEXA gene has been reported previously in association with Tay Sachs disease (Akli et al., 1991; Mules et al., 1992). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R137X variant 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. We interpret R137X as a pathogenic variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000255817 SCV000331825 pathogenic not provided 2015-11-06 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000004110 SCV000893377 pathogenic Tay-Sachs disease 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000004110 SCV000917518 pathogenic Tay-Sachs disease 2018-07-23 criteria provided, single submitter clinical testing Variant summary: HEXA c.409C>T (p.Arg137X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.9e-05 in 277008 control chromosomes. c.409C>T has been reported in the literature in individuals affected with Tay-Sachs Disease (Gort_2012, Mules_1992, Ozkara_1998, Zampieri_2012). These data indicate that the variant is associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000004110 SCV001209223 pathogenic Tay-Sachs disease 2019-10-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg137*) in the HEXA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs121907962, ExAC 0.003%). This variant has been observed in combination with another HEXA variant in individuals affected with hexosaminidase A deficiency (PMID: 1837283, 18648917, 22441121, 22789865). ClinVar contains an entry for this variant (Variation ID: 3904). This variant has been reported to affect HEXA protein function (PMID: 1837283). Loss-of-function variants in HEXA are known to be pathogenic (PMID: 1833974, 8490625). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004110 SCV000024276 pathogenic Tay-Sachs disease 1992-04-01 no assertion criteria provided literature only

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