Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000150720 | SCV000198138 | likely pathogenic | Rare genetic deafness | 2016-05-18 | criteria provided, single submitter | clinical testing | The p.Thr41Lys variant in GIPC3 has been previously identified in one consanguin eous Saudi Arabian family with prelingual severe to profound sensorineural heari ng loss and was not identified among 400 ethnically matched control chromosomes (Ramzan 2013). The Thr41Lys variant segregated in the homozygous state in five a ffected siblings, while the parents and two unaffected siblings were either hete rozygous for the variant or were wild-type (Ramzan 2013). However, the reported segregation data cannot rule out linkage disequilibrium between the Thr41Lys var iant and another causative variant. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pa thogenic based on the segregation data from the previously reported family. |
| Gene |
RCV000413083 | SCV000491294 | likely pathogenic | not provided | 2023-03-08 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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: 31589614, 32864763, 23510777, 32747562) |
| Kariminejad - |
RCV004700476 | SCV000992247 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 15 | 2023-06-17 | criteria provided, single submitter | clinical testing | Now, we have found stronger evidence of pathogenicity and changed this variant classification from uncertain significance to likely pathogenic (PM2,PM3_Moderate ,PP3_Moderate; according to ACMG Guidelines, 2015) |
| Labcorp Genetics |
RCV000413083 | SCV004297979 | pathogenic | not provided | 2023-05-21 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 GIPC3 protein function. ClinVar contains an entry for this variant (Variation ID: 163502). This missense change has been observed in individuals with nonsyndromic deafness (PMID: 23510777, 32747562, 32864763). It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 41 of the GIPC3 protein (p.Thr41Lys). |