Submissions for variant NM_000314.8(PTEN):c.235G>A (p.Ala79Thr) (rs202004587)

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PTEN Variant Curation Expert Panel	RCV000123046	SCV000840467	likely benign	PTEN hamartoma tumor syndrome	2018-04-06	reviewed by expert panel	curation	PTEN c.235G>A (p.A79T) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BS1: Allele frequency of 0.0045 (0.45%, 9/1984 alleles) in the GME variome. (PMID 27428751) BS2_P: Meets criteria for BS2 (observed in the homozygous state in at least one healthy or PHTS-unaffected individual) but BS1 is also applied. (Internal laboratory contributor(s) SCV000222198.12) 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.
Invitae	RCV000123046	SCV000166341	benign	PTEN hamartoma tumor syndrome	2019-12-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000129085	SCV000183790	likely benign	Hereditary cancer-predisposing syndrome	2019-01-11	criteria provided, single submitter	clinical testing	In silico models in agreement (benign);Other data supporting benign classification
GeneDx	RCV000034594	SCV000222198	likely benign	not provided	2018-07-18	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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia	RCV000123046	SCV000257666	uncertain significance	PTEN hamartoma tumor syndrome	2015-07-10	criteria provided, single submitter	clinical testing
Counsyl	RCV000409443	SCV000487786	uncertain significance	Cowden syndrome 1	2015-11-17	criteria provided, single submitter	clinical testing
Fulgent Genetics,Fulgent Genetics	RCV000515193	SCV000611427	uncertain significance	Endometrial carcinoma; Macrocephaly/autism syndrome; Meningioma, familial; Squamous cell carcinoma of the head and neck; Bannayan-Riley-Ruvalcaba syndrome; Malignant tumor of prostate; Thyroid cancer, nonmedullary, 2; VACTERL association with hydrocephalus; Glioma susceptibility 2; Cowden syndrome 1; Cutaneous malignant melanoma 1	2017-05-23	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000626250	SCV000746903	uncertain significance	Macrocephaly/autism syndrome	2017-12-18	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000034594	SCV000806056	uncertain significance	not provided	2014-09-18	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000129085	SCV000822140	uncertain significance	Hereditary cancer-predisposing syndrome	2018-08-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000123046	SCV000838417	uncertain significance	PTEN hamartoma tumor syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000034594	SCV000888591	likely benign	not provided	2019-04-16	criteria provided, single submitter	clinical testing
Color	RCV000129085	SCV000902713	likely benign	Hereditary cancer-predisposing syndrome	2016-04-11	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Strasbourg University Hospital	RCV001257777	SCV001434590	uncertain significance	Intellectual disability	2020-04-20	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health	RCV000034594	SCV000043462	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
AlTemaimi Lab, Faculty of Medicine,Kuwait University	RCV000409443	SCV000577862	pathogenic	Cowden syndrome 1	2017-05-19	no assertion criteria provided	clinical testing	CMT panel and gene duplication assays were negative and investigative exome sequencing was conducted. Clinical presentation is 80% match with Cowden Syndrome (exception unilateral pes cavus).