Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000217775 | SCV000271599 | uncertain significance | not specified | 2016-03-08 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Pro621Thr variant in COL11A2 has been reported in the homozygous state in one Iranian ind ividual with hearing loss and segregated with disease in 4 affected relatives wi thin the individual's consanguineous family (Chen 2005). This variant has also b een identified in 10/14172 South Asian chromosomes by the Exome Aggregation Cons ortium (ExAC, http://exac.broadinstitute.org; dbSNP rs121912952). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that the p.Pro621Thr variant may impact the p rotein, though this information is not predictive enough to determine pathogenic ity. However, there is limited data associating variants in the COL11A2 gene wit h autosomal recessive nonsyndromic hearing loss. Only three consanguineous famil ies with homozygous variants in COL11A2 have been described, including the famil y described above with the p.Pro621THr variant. In addition, there is limited da ta of the general populations from which these families are from (Iranian, Tunis ian, and Turkish; Chen 2005, Chakchouk 2015). In summary, although there is some suspicion for a pathogenic role, the clinical significance of this variant is u ncertain. |
| Ce |
RCV000584845 | SCV000693209 | likely pathogenic | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | COL11A2: PP1:Strong, PM2 |
| Department of Otolaryngology – Head & Neck Surgery, |
RCV001375391 | SCV001571824 | uncertain significance | Hearing impairment | 2021-04-12 | criteria provided, single submitter | clinical testing | PS1_Moderate, PM2_Moderate |
| Gene |
RCV000584845 | SCV001783298 | uncertain significance | not provided | 2022-05-24 | criteria provided, single submitter | clinical testing | Reported in the homozygous state in five relatives from a consanguineous family with non-syndromic hearing loss (Chen et al., 2005); 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: 34426522, 16033917) |
| Invitae | RCV000584845 | SCV002233563 | pathogenic | not provided | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 621 of the COL11A2 protein (p.Pro621Thr). This variant is present in population databases (rs121912952, gnomAD 0.04%). This missense change has been observed in individual(s) with autosomal recessive non-syndromic deafness (PMID: 16033917). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17129). 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 COL11A2 protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| MGZ Medical Genetics Center | RCV000018667 | SCV002581240 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 53 | 2022-02-01 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000018667 | SCV000038950 | pathogenic | Autosomal recessive nonsyndromic hearing loss 53 | 2005-10-01 | no assertion criteria provided | literature only |