ClinVar Miner

Submissions for variant NM_001377.3(DYNC2H1):c.1774C>T (p.Leu592Phe)

gnomAD frequency: 0.00052  dbSNP: rs180861816
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195758 SCV000254666 uncertain significance Jeune thoracic dystrophy 2022-09-16 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 592 of the DYNC2H1 protein (p.Leu592Phe). This variant is present in population databases (rs180861816, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 216489). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DYNC2H1 protein function. 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.
Illumina Laboratory Services, Illumina RCV001106879 SCV001263988 uncertain significance Asphyxiating thoracic dystrophy 3 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 RCV001561120 SCV001783658 uncertain significance not provided 2023-06-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 34490615, 36011280)
Blueprint Genetics RCV001561120 SCV001832475 uncertain significance not provided 2019-11-30 criteria provided, single submitter clinical testing
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital RCV001106879 SCV001984082 uncertain significance Asphyxiating thoracic dystrophy 3 2020-03-25 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV001249319 SCV001423283 not provided DYNC2H1-Related Disorder no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 12-11-2017 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001251983 SCV001427729 uncertain significance Intellectual disability 2019-01-01 no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001561120 SCV001954257 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001561120 SCV001971742 uncertain significance not provided no assertion criteria provided clinical testing

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