Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158464 | SCV000208399 | uncertain significance | not provided | 2011-12-12 | criteria provided, single submitter | clinical testing | This variant is denoted p.Asn143Ser (N143S) at the protein level and c.428 A>G at the cDNA level. The clinical significance of this variant is currently not clear. Asn143Ser has not been reported previously as a disease-causing mutation or as a rare benign polymorphism, to our knowledge. The following information suggests that Asn143Ser may be disease-causing. The Asn143Ser variant was not observed in up to 200 control alleles from individuals of Caucasian ancestry, indicating it is not a common benign polymorphism in this population. Mutations in nearby codons (Ala140Thr, Ile154Thr) have been reported in association with HCM, supporting the functional importance of this region of the protein. However, the following evidence suggests that Asn143Ser in the MYBPC3 gene may be a benign variant. Asn143Ser results in a conservative amino acid substitution of one uncharged, polar amino acid with another at a position that is not highly conserved throughout evolution. In silico analysis predicts this change is benign to the structure/function of the protein. With the clinical and molecular information available at this time, we cannot unequivocally determine if the Asn143Ser variant in the MYBCP3 gene is a disease-causing mutation or a rare benign polymorphism. The variant is found in HCM panel(s). |