ClinVar Miner

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

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Total submissions: 6
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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

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