Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000624102 | SCV000742192 | likely pathogenic | Inborn genetic diseases | 2020-06-04 | criteria provided, single submitter | clinical testing | This alteration results in an elongated protein: The c.616_632del17 (p.E206Rfs*130) alteration, located in coding exon 2 of the MARCKS gene, results from a deletion of 17 nucleotides from position 616 to 632, causing a translational frameshift with a predicted alternate stop codon. Frameshifts are typically deleterious in nature; however, this frameshift occurs at the 3' terminus of MARCKS, is not expected to trigger nonsense-mediated mRNA decay, and an altered mutant protein could still be expressed (Maquat, 2004). This frameshift changes the remaining 127 amino acids of the protein and elongates the protein by 2 amino acids. The exact functional impact of these altered amino acids is unknown at this time. This alteration is located in a functionally important protein domain: The p.E206RFS*130 amino acid starts in an observed calmodulin binding region, which is known be required for MARCKS protein function (Naim, 1992; Hartwig, 1992; Gallant, 2005). Based on the available evidence, this alteration is classified as likely pathogenic. |