Submissions for variant NM_001165927.1(MKS1):c.827A>G (p.Asp276Gly) (rs151023718)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	RCV000514949	SCV000610371	uncertain significance	not provided	2017-09-11	criteria provided, single submitter	clinical testing
Counsyl	RCV000664898	SCV000788928	uncertain significance	Bardet-Biedl syndrome 13; Meckel syndrome type 1; Joubert syndrome 28	2017-01-03	criteria provided, single submitter	clinical testing
Invitae	RCV000690393	SCV000818077	uncertain significance	Joubert syndrome; Meckel-Gruber syndrome	2019-12-16	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid with glycine at codon 286 of the MKS1 protein (p.Asp286Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs151023718, ExAC 0.09%). This variant has been observed in several individuals affected with ciliopathies, however a second allele was not found and in at least one individual pathogenic variants were found in a different gene (PMID: 18327255, 28224992, 21068128, 21258341). ClinVar contains an entry for this variant (Variation ID: 445724). Experimental studies have shown that this missense change has a moderate disrupting effect on protein function (PMID: 18327255). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000514949	SCV000854879	uncertain significance	not provided	2018-05-08	criteria provided, single submitter	clinical testing
Mendelics	RCV000989953	SCV001140699	uncertain significance	Bardet-Biedl syndrome 13	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001126360	SCV001285541	uncertain significance	Meckel syndrome type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina	RCV000989953	SCV001285542	uncertain significance	Bardet-Biedl syndrome 13	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet	RCV000514949	SCV000926866	likely pathogenic	not provided	2018-04-01	no assertion criteria provided	research