ClinVar Miner

Submissions for variant NM_004239.4(TRIP11):c.382G>T (p.Ala128Ser) (rs141553918)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000178208 SCV000230227 uncertain significance not provided 2017-10-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000684947 SCV000389599 uncertain significance Achondrogenesis, type IA 2018-01-12 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.
Invitae RCV000684947 SCV000812412 uncertain significance Achondrogenesis, type IA 2019-03-06 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 128 of the TRIP11 protein (p.Ala128Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs141553918, ExAC 0.1%). This variant has not been reported in the literature in individuals with TRIP11-related disease. ClinVar contains an entry for this variant (Variation ID: 197230). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000178208 SCV000884732 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing The TRIP11 c.382G>T; p.Ala128Ser variant (rs141553918), to our knowledge, is not described in the medical literature but is listed as a variant of uncertain clinical significance in ClinVar (Variation ID: 197230). It is observed in the European (Non-Finnish) population at an overall frequency of 0.15% (195/126594 alleles, 1 homozygote) in the Genome Aggregation Database. The alanine at codon 128 is moderately conserved, but computational algorithms (PolyPhen-2, SIFT) predict that this variant is tolerated. Based on available information, this variant is considered likely benign.

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