Submissions for variant NM_000314.8(PTEN):c.78C>T (p.Thr26=)

gnomAD frequency: 0.00001  dbSNP: rs786201280

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clingen PTEN Variant Curation Expert Panel, Clingen	RCV000204337	SCV000840494	uncertain significance	PTEN hamartoma tumor syndrome	2020-03-23	reviewed by expert panel	curation	PTEN c.78C>T (p.T26=) is currently classified as a variant of uncertain significance 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: Present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533). BP7: Variant is synonymous (silent), nucleotide is not conserved, and no splicing impact is predicted.
Ambry Genetics	RCV000163228	SCV000213753	likely benign	Hereditary cancer-predisposing syndrome	2014-09-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV000204337	SCV000262250	likely benign	PTEN hamartoma tumor syndrome	2024-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000679314	SCV000279427	likely benign	not provided	2020-03-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27978560, 30311380, 30287823)
Counsyl	RCV000662592	SCV000785221	uncertain significance	Cowden syndrome 1	2017-06-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000679314	SCV000806064	uncertain significance	not provided	2018-01-04	criteria provided, single submitter	clinical testing
Mendelics	RCV000204337	SCV000838415	uncertain significance	PTEN hamartoma tumor syndrome	2018-07-02	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000679314	SCV000884427	benign	not provided	2017-06-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163228	SCV000905155	likely benign	Hereditary cancer-predisposing syndrome	2015-08-17	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000662592	SCV004019950	uncertain significance	Cowden syndrome 1	2023-04-05	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000679314	SCV004219144	uncertain significance	not provided	2023-08-16	criteria provided, single submitter	clinical testing	In the published literature, this variant has been reported in individuals with breast cancer (PMID: 30287823 (2018)) and colorectal cancer (PMID: 27978560 (2016)). The frequency of this variant in the general population, 0.000032 (1/31410 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect PTEN mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.