Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000512900 | SCV000608704 | uncertain significance | not provided | 2017-05-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000706990 | SCV000836066 | uncertain significance | Branchiootic syndrome 3; Autosomal dominant nonsyndromic hearing loss 23 | 2022-09-23 | criteria provided, single submitter | clinical testing | 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt SIX1 protein function. ClinVar contains an entry for this variant (Variation ID: 444331). This variant has not been reported in the literature in individuals affected with SIX1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 64 of the SIX1 protein (p.Arg64His). |
Department of Otolaryngology – Head & Neck Surgery, |
RCV001375398 | SCV001571879 | uncertain significance | Hearing impairment | 2021-04-12 | criteria provided, single submitter | clinical testing | PM2_Moderate, PP3_Supporting |
Gene |
RCV000512900 | SCV001813522 | likely benign | not provided | 2020-03-12 | 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 |
Ambry Genetics | RCV002524959 | SCV003721477 | uncertain significance | Inborn genetic diseases | 2022-01-18 | criteria provided, single submitter | clinical testing | The c.191G>A (p.R64H) alteration is located in exon 1 (coding exon 1) of the SIX1 gene. This alteration results from a G to A substitution at nucleotide position 191, causing the arginine (R) at amino acid position 64 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |