Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000731326 | SCV000859131 | uncertain significance | not provided | 2018-01-30 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000731326 | SCV001986338 | uncertain significance | not provided | 2019-04-26 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; A published functional study suggests that P363L is a hypomorphic variant (Zaghloul et al., 2010); Identified in an individual with Bardet-Biedl syndrome who also had the S329L and c.271dupT variants, but it is not known whether these variants occurred on the same (in cis) or on different (in trans) chromosomes (Stoetzel et al., 2006); This variant is associated with the following publications: (PMID: 20498079, 16582908) |
Labcorp Genetics |
RCV002535203 | SCV003516972 | uncertain significance | Bardet-Biedl syndrome | 2024-05-18 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 363 of the BBS10 protein (p.Pro363Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 16582908). ClinVar contains an entry for this variant (Variation ID: 595700). 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 BBS10 protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BBS10 function (PMID: 20080638, 20498079). 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. |