Submissions for variant NM_001126049.1(KLLN):c.-840G>A (rs563841270)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PTEN Variant Curation Expert Panel	RCV000233564	SCV000863474	likely benign	PTEN hamartoma tumor syndrome	2018-04-06	reviewed by expert panel	curation	PTEN c.-1142C>T (NC_000010.10:g.89623084C>T) meets criteria to be classified as likely benign 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). BS1: Allele frequency of 0.0049 (0.49%, 8/1622 alleles) in the East Asian subpopulation of the gnomAD cohort. (PMID 27535533) BP2: Observed in trans with a pathogenic or likely pathogenic PTEN variant, at least three observations in cis and/or phase unknown with different pathogenic/likely pathogenic PTEN variants. (Internal laboratory contributors SCV000187279.1, SCV000149465.6)
GeneDx	RCV000201311	SCV000149465	likely benign	not specified	2016-06-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000115556	SCV000187279	uncertain significance	Hereditary cancer-predisposing syndrome	2014-03-10	criteria provided, single submitter	clinical testing
Invitae	RCV000233564	SCV000284571	likely benign	PTEN hamartoma tumor syndrome	2016-03-18	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000590028	SCV000696527	likely benign	not provided	2017-01-20	criteria provided, single submitter	clinical testing	Variant summary: The PTEN variant c.-1142C>T (also known as c.-1143C>T) located in the 5' UTR region of PTEN causes an alteration of a non-conserved nucleotide. The variant of interest was observed in the 1000 Gs control population with an allele frequency of 12/5044 (1/420, 1 homozygote), predominantly in the East Asian cohort, 8/1008 (1/125, 1 homozygote), which exceeds the estimated maximal expected allele frequency for a pathogenic PTEN variant of 1/158730. Therefore, suggesting this variant is likely a benign polymorphism for in population(s) of East Asian origin. However, these observations do need to be cautiously considered due to the PTEN pseudogene possibly being captured. A functional study, Ohsaka_2010, found the variant not to affect luciferase activity, although they do state the outcome is cell type dependent. In addition, multiple clinical diagnostic laboratories classified this variant as "likely benign" or "uncertain significance." Therefore, the variant of interest has been classified as "likely benign."
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000590028	SCV000888582	benign	not provided	2018-06-19	criteria provided, single submitter	clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000201311	SCV000691986	uncertain significance	not specified		no assertion criteria provided	clinical testing