ClinVar Miner

Submissions for variant NM_004568.6(SERPINB6):c.251C>T (p.Thr84Met)

dbSNP: rs538616923
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000611948 SCV000712060 uncertain significance not specified 2016-04-25 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Thr84Met vari ant in SERPINB6 has not been previously reported in individuals with hearing los s, but has been identified in 0.1% (12/16510) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs5386 16923). Threonine (Thr) at position 84 is not conserved in mammals or evolutiona rily distant species and one mammal (rabbit) carries a Methionine (Met), raising the possibility that this change may be tolerated. Additional computational pr ediction tools suggest that the p.Thr84Met variant may not impact the protein, t hough this information is not predictive enough to rule out pathogenicity. In su mmary, while the clinical significance of the p.Thr84Met variant is uncertain, t hese data suggest that it is more likely to be benign.
Fulgent Genetics, Fulgent Genetics RCV000764642 SCV000895750 uncertain significance Autosomal recessive nonsyndromic hearing loss 91 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV002529313 SCV003501246 uncertain significance not provided 2022-07-11 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 84 of the SERPINB6 protein (p.Thr84Met). This variant is present in population databases (rs538616923, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SERPINB6-related conditions. ClinVar contains an entry for this variant (Variation ID: 504995). 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: "Possibly 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.

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