Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000500081 | SCV000593607 | uncertain significance | not specified | 2017-04-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001054420 | SCV001218733 | uncertain significance | Bardet-Biedl syndrome | 2022-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 459 of the BBS7 protein (p.Arg459Cys). This variant is present in population databases (rs150743868, gnomAD 0.05%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 30718709). ClinVar contains an entry for this variant (Variation ID: 434498). 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 expected to disrupt BBS7 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. |
Illumina Laboratory Services, |
RCV001144794 | SCV001305409 | uncertain significance | Bardet-Biedl syndrome 7 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Fulgent Genetics, |
RCV001144794 | SCV002782374 | uncertain significance | Bardet-Biedl syndrome 7 | 2022-04-06 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002527207 | SCV003688469 | uncertain significance | Inborn genetic diseases | 2022-07-28 | criteria provided, single submitter | clinical testing | The c.1375C>T (p.R459C) alteration is located in exon 14 (coding exon 14) of the BBS7 gene. This alteration results from a C to T substitution at nucleotide position 1375, causing the arginine (R) at amino acid position 459 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Preventiongenetics, |
RCV003409691 | SCV004109905 | uncertain significance | BBS7-related condition | 2023-06-19 | criteria provided, single submitter | clinical testing | The BBS7 c.1375C>T variant is predicted to result in the amino acid substitution p.Arg459Cys. This variant was found in the heterozygous state in an individual with retinitis pigmentosa; however, a second variant was not identified (Table S4 - Jespersgaard et al. 2019. PubMed ID: 30718709).This variant is reported in 0.048% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-122756435-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Department of Clinical Genetics, |
RCV000787793 | SCV000926803 | likely pathogenic | Retinitis pigmentosa | 2018-04-01 | no assertion criteria provided | research |