Submissions for variant NM_000548.5(TSC2):c.5150T>C (p.Leu1717Pro) (rs45517398)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000190040	SCV000243714	pathogenic	not provided	2014-02-21	criteria provided, single submitter	clinical testing	p.Leu1717Pro (CTG>CCG): c.5150 T>C in exon 40 of the TSC2 gene (NM_000548.3). The Leu1717Pro missense mutation in the TSC2 gene has been reported previously as a de novo mutation in a patient with cardiac rhabdomyomas, hypopigmentation of the skin, subependymal nodules, and seizures beginning at 1 year of age (Chen et al., 2005). This mutation is reported in the TSC2 LOVD database in three additional patients. It 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. Leu1717Pro is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is highly conserved across species and many other missense mutations associated with TSC2-related disorders have been reported in this region of the protein. The variant is found in INFANT-EPI panel(s).
Tuberous sclerosis database (TSC2)	RCV000042612	SCV000066406	not provided	Tuberous sclerosis syndrome		no assertion provided	curation