Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000611948 | SCV006157623 | uncertain significance | not specified | 2025-05-05 | criteria provided, single submitter | clinical testing | The c.251C>T (p.T84M) alteration is located in exon 3 (coding exon 2) of the SERPINB6 gene. This alteration results from a C to T substitution at nucleotide position 251, causing the threonine (T) at amino acid position 84 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV002529313 | SCV005384276 | uncertain significance | not provided | 2024-01-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV002529313 | SCV003501246 | uncertain significance | not provided | 2025-03-31 | 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). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SERPINB6 protein function with a negative predictive value of 80%. 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. |
| Fulgent Genetics, |
RCV000764642 | SCV000895750 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 91 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular 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. |