ClinVar Miner

Submissions for variant NM_017775.4(TTC19):c.146C>T (p.Pro49Leu)

gnomAD frequency: 0.00141  dbSNP: rs537063695
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000325478 SCV000400814 uncertain significance Mitochondrial complex III deficiency nuclear 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.
GeneDx RCV000676981 SCV000517347 likely benign not provided 2020-07-10 criteria provided, single submitter clinical testing
Invitae RCV000676981 SCV003258224 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 49 of the TTC19 protein (p.Pro49Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TTC19-related conditions. ClinVar contains an entry for this variant (Variation ID: 321941). 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. 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.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000325478 SCV004047486 uncertain significance Mitochondrial complex III deficiency nuclear type 2 criteria provided, single submitter clinical testing The missense variant in c.146C>T (p.Pro49Leu) in TTC19 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Pro49Leu variant is reported with the allele frequency of 0.08000% in gnomAD Exome and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain significance/ Likely benign. The amino acid Pro at position 49 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as uncertain significance.
Mayo Clinic Laboratories, Mayo Clinic RCV000676981 SCV000802808 uncertain significance not provided 2017-08-22 no assertion criteria provided clinical testing

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