Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003595704 | SCV001417221 | uncertain significance | Ichthyosis linearis circumflexa | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 561 of the SPINK5 protein (p.Glu561Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with chronic otitis media, asthma, dry skin, and eczema (PMID: 32709676). ClinVar contains an entry for this variant (Variation ID: 918078). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SPINK5 protein function. 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. |
Gene |
RCV001545943 | SCV001765369 | uncertain significance | not provided | 2020-11-20 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32709676) |
Santos- |
RCV001260957 | SCV001338935 | pathogenic | Susceptibility to nonsyndromic otitis media | 2020-04-18 | no assertion criteria provided | research | |
University of Washington Center for Mendelian Genomics, |
RCV001543375 | SCV001761933 | likely pathogenic | Otitis media, susceptibility to | no assertion criteria provided | research |