Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000183306 | SCV000235733 | uncertain significance | not provided | 2017-04-21 | criteria provided, single submitter | clinical testing | The c.795dupT variant in the ANKRD1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. It results in replacement of the Lysine codon 266 with a premature STOP codon, and is expected to result in an abnormal, truncated protein or in absence of protein from this allele due to mRNA decay. To date, the only pathogenic mutations in the ANKRD1 gene reported in association with cardiomyopathy have been missense mutations, which were found to alter the function and/or localization of CARP in cardiomyocytes, and were hypothesized to interfere with the function of protein partners in the the titin-N2A mechanosensory complex in a dominant negative manner (Moulik M et al., 2009; Arimura T et al., 2009; Duboscq-Bidot L et al., 2009). It is unknown if the c.795dupT variant may also diminish interactions with the titin-N2A mechanosensory complex, as has been demonstrated for reported missense mutations. Therefore, with the clinical and molecular information available at this time, we cannot unequivocally determine the clinical significance of the c.795dupT variant in the ANKRD1 gene. |
Ambry Genetics | RCV004639165 | SCV005141890 | uncertain significance | Cardiovascular phenotype | 2024-06-03 | criteria provided, single submitter | clinical testing | The c.795dupT variant, located in coding exon 8 of the ANKRD1 gene, results from a duplication of T at nucleotide position 795, causing a translational frameshift with a predicted alternate stop codon (p.K266*). This alteration is expected to result in protein truncation or nonsense-mediated mRNA decay. However, loss of function of ANKRD1 has not been established as a mechanism of disease. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |