Submissions for variant NM_000314.7(PTEN):c.740T>C (p.Leu247Ser) (rs1057519368)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PTEN Variant Curation Expert Panel	RCV000790884	SCV000930113	likely pathogenic	PTEN hamartoma tumor syndrome	2019-06-25	reviewed by expert panel	curation	PTEN c.740T>C (p.Leu247Ser) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PM2: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID 28086757) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 28086757)
Department of Pediatrics and Neonatology,Nagoya City University Graduate School of Medical Sciences	RCV000416564	SCV000264589	pathogenic	Macrocephaly/autism syndrome	2015-11-01	no assertion criteria provided	research	Patient, a 4 year-old girl, showed mild developmental delay, hypotonia, and dysmorphic facial features. Her last head circumference was 56.5 cm (+4.0SD). This mutation was confirmed de novo. The expression level of phosphorylated S6 ribosomal protein in her lymphoblastoid cell line was elevated.