Submissions for variant NM_153704.6(TMEM67):c.653G>C (p.Gly218Ala) (rs202036490)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519954	SCV000617745	uncertain significance	not provided	2018-12-18	criteria provided, single submitter	clinical testing	The G218A variant has been previously reported to have occurred in cis with a TMEM67 S320C variant in an individual with Bardet-Biedl syndrome (BBS), a complex multi-organ ciliopathy, who was also homozygous for the E1903X nonsense variant in the CEP290 gene (Leitch et al., 2008). Functional studies demonstrated that the G218A variant had a minimal effect on protein function (Leitch et al., 2008). The G218A variant is observed in 30/126,448 (0.02%) alleles from individuals of non-Finnish European background (Lek et al., 2016). The G218A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina	RCV001165118	SCV001327287	uncertain significance	Nephronophthisis 11	2017-04-28	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	RCV001165119	SCV001327288	uncertain significance	Joubert syndrome 6	2017-04-28	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	RCV001165120	SCV001327289	uncertain significance	Meckel syndrome, type 3	2017-04-28	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.
Centre for Mendelian Genomics,University Medical Centre Ljubljana	RCV001198569	SCV001369558	uncertain significance	RHYNS syndrome	2019-10-02	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001165120	SCV001440695	uncertain significance	Meckel syndrome, type 3	2019-01-01	criteria provided, single submitter	clinical testing