ClinVar Miner

Submissions for variant NM_001173990.3(TMEM216):c.140T>C (p.Val47Ala) (rs762918371)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000401686 SCV000344452 uncertain significance not provided 2018-06-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000291175 SCV000372626 uncertain significance Meckel syndrome, type 2 2018-01-13 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.
Illumina Clinical Services Laboratory,Illumina RCV000345935 SCV000372627 uncertain significance Joubert syndrome 2 2018-01-13 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,Fulgent Genetics RCV000763754 SCV000894640 uncertain significance Joubert syndrome 2; Meckel syndrome, type 2 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001240998 SCV001413987 uncertain significance Joubert syndrome 2019-11-18 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 47 of the TMEM216 protein (p.Val47Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs762918371, ExAC 0.2%). This variant has not been reported in the literature in individuals with TMEM216-related disease. ClinVar contains an entry for this variant (Variation ID: 289981). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

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