Submissions for variant NM_024649.5(BBS1):c.1139G>A (p.Arg380Gln)

gnomAD frequency: 0.00002  dbSNP: rs758139447

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000196228	SCV000255070	uncertain significance	Bardet-Biedl syndrome	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 380 of the BBS1 protein (p.Arg380Gln). This variant is present in population databases (rs758139447, gnomAD 0.02%). This missense change has been observed in individual(s) with BBS1-related conditions (PMID: 27434533). ClinVar contains an entry for this variant (Variation ID: 216740). 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 BBS1 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.
GeneDx	RCV000434974	SCV000536422	uncertain significance	not provided	2023-10-10	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27434533)
Counsyl	RCV000709655	SCV000794591	uncertain significance	Bardet-Biedl syndrome 1	2017-10-02	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000709655	SCV001520772	uncertain significance	Bardet-Biedl syndrome 1	2019-07-30	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002229495	SCV002511879	uncertain significance	not specified	2022-04-05	criteria provided, single submitter	clinical testing	Variant summary: BBS1 c.1139G>A (p.Arg380Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251472 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1139G>A has been reported in the literature in one individual affected with Joubert syndrome without co-segregation evidence. This report does not provide unequivocal conclusions about association of the variant with Bardet-Biedl Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV000709655	SCV002793667	uncertain significance	Bardet-Biedl syndrome 1	2021-12-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000434974	SCV004136981	uncertain significance	not provided	2022-09-01	criteria provided, single submitter	clinical testing	BBS1: PM2:Supporting
Natera, Inc.	RCV000709655	SCV002094758	uncertain significance	Bardet-Biedl syndrome 1	2020-01-31	no assertion criteria provided	clinical testing