Submissions for variant NM_001126049.2(KLLN):c.-812G>A

dbSNP: rs587779981

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clingen PTEN Variant Curation Expert Panel, Clingen	RCV000710304	SCV000840482	likely benign	PTEN hamartoma tumor syndrome	2020-03-23	reviewed by expert panel	curation	PTEN c.-1170C>T (NC_000010.10:g. 89623056C>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_P: Allele frequency of 0.0002477 (0.02477%, 16/64,586 alleles) in the European subpopulation of the gnomAD cohort. (PMID 27535533) BP5: Variant found in multiple cases with alternate molecular basis for disease. (Internal laboratory contributor(s) SCV000149466.6, SCV000184146.1)
GeneDx	RCV000734292	SCV000149466	likely benign	not provided	2021-04-15	criteria provided, single submitter	clinical testing	Also known as c.-1170C>T; Observed in at least three individuals, two of whom were reported to have a history of breast and/or thyroid cancer; however, the proband either did not meet full International Cowden Syndrome Consortium operational diagnostic criteria or details were not provided on their specific features (Tan 2011, Wang 2011, Nizialek 2015); No data available from control populations to assess the frequency of this variant; Observed in multiple individuals referred for genetic testing at GeneDx who had a different genetic etiology for the phenotype; This variant is associated with the following publications: (PMID: 21532617, 21194675, 30311380, 25669429)
Ambry Genetics	RCV000115557	SCV000184146	uncertain significance	Hereditary cancer-predisposing syndrome	2014-03-05	criteria provided, single submitter	clinical testing
Counsyl	RCV000409641	SCV000487866	uncertain significance	Cowden syndrome 1	2015-11-25	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000115557	SCV000803171	uncertain significance	Hereditary cancer-predisposing syndrome	2018-05-23	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000734292	SCV000862422	uncertain significance	not provided	2018-07-13	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000734292	SCV000888583	uncertain significance	not provided	2019-11-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935099	SCV004760833	likely benign	PTEN-related condition	2020-08-18	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).