Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002318658 | SCV000849918 | uncertain significance | Inborn genetic diseases | 2017-05-31 | criteria provided, single submitter | clinical testing | The p.Y1380* variant (also known as c.4140T>G), located in coding exon 19 of the DYNC1H1 gene, results from a T to G substitution at nucleotide position 4140. This changes the amino acid from a tyrosine to a stop codon within coding exon 19. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of DYNC1H1 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222614 | SCV002500803 | uncertain significance | not specified | 2022-03-31 | criteria provided, single submitter | clinical testing | Variant summary: DYNC1H1 c.4140T>G (p.Tyr1380X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay. However, loss-of-function is not currently an established mechanism of disease for this gene. The variant was absent in 251494 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4140T>G in individuals affected with DYNC1H1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |