ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.912CTT[1] (p.Phe305del) (rs121907960)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169148 SCV000220373 likely pathogenic Tay-Sachs disease 2014-06-05 criteria provided, single submitter literature only
Ambry Genetics RCV000622988 SCV000742705 pathogenic Inborn genetic diseases 2017-07-25 criteria provided, single submitter clinical testing
Invitae RCV000169148 SCV000933426 pathogenic Tay-Sachs disease 2018-10-23 criteria provided, single submitter clinical testing This variant, c.915_917delCTT, results in the deletion of 1 amino acid(s) of the HEXA protein (p.Phe305del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs778155650, ExAC 0.02%). This variant has been reported as in combination with another HEXA variant in several individuals affected with Tay-Sachs disease (PMID: 16088929, 1837283) as well as affected individuals in whom the second allele was not identified (PMID: 1837283, 1825014). This variant is common in the Moroccan population (PMID: 1322637, 1825014)  ClinVar contains an entry for this variant (Variation ID: 188812). This variant is also know as p.F304del in the literature. Experimental studies have shown that this deletion causes reduced enzyme activity when expressed in COS 1 cells (PMID: 1825014). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001545560 SCV001764916 pathogenic not provided 2019-11-29 criteria provided, single submitter clinical testing Transfection in COS-1 cells of the mutant protein demonstrated an impairment in the alpha subunit of beta-hexosaminidase A, resulting in an absence of enzyme activity (Navon et al., 1991); In-frame deletion of 1 amino acids in a non-repeat region predicted to critically alter the protein; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported previously in multiple individuals with infantile-onset Tay Sachs disease who were either homozygous or compound heterozygous (Akli et al, 1991; Gort et al., 2012); This variant is associated with the following publications: (PMID: 22789865, 1837283, 16088929, 1825014, 1322637)
OMIM RCV000169148 SCV000024275 pathogenic Tay-Sachs disease 1992-08-01 no assertion criteria provided literature only

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