Submissions for variant NM_170707.4(LMNA):c.64T>G (p.Ser22Ala)

dbSNP: rs794728599

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182379	SCV000234716	likely pathogenic	not provided	2014-02-20	criteria provided, single submitter	clinical testing	p.Ser22Ala (TCG>GCG): c.64 T>G in exon 1 of the LMNA gene (NM_170707.2). The S22A variant in the LMNA gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The S22A variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The S22 residue is conserved across species. A mutation affecting the same residue (S22L) and a mutation affecting a nearby residue (R25C) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, the S22A variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, while S22A is a good candidate for a disease-causing mutation, with the information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in DCM-CRDM panel(s).