ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.1416G>C (p.Arg472Ser)

gnomAD frequency: 0.00012  dbSNP: rs369117208
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670765 SCV000795661 uncertain significance Tay-Sachs disease 2017-11-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781462 SCV000919499 uncertain significance not specified 2017-12-07 criteria provided, single submitter clinical testing Variant summary: The HEXA c.1416G>C (p.Arg472Ser) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 18/276566 control chromosomes at a frequency of 0.0000651, which does not exceed the estimated maximal expected allele frequency of a pathogenic HEXA variant (0.0013975). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000670765 SCV001203703 uncertain significance Tay-Sachs disease 2022-08-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 472 of the HEXA protein (p.Arg472Ser). This variant is present in population databases (rs369117208, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with HEXA-related conditions. ClinVar contains an entry for this variant (Variation ID: 555026). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002388180 SCV002698520 uncertain significance Inborn genetic diseases 2017-07-01 criteria provided, single submitter clinical testing The p.R472S variant (also known as c.1416G>C), located in coding exon 12 of the HEXA gene, results from a G to C substitution at nucleotide position 1416. The arginine at codon 472 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000670765 SCV002085665 uncertain significance Tay-Sachs disease 2017-04-21 no assertion criteria provided clinical testing

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