Submissions for variant NM_001126049.2(KLLN):c.-794_-783del

dbSNP: rs587781340

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clingen PTEN Variant Curation Expert Panel, Clingen	RCV000790891	SCV000930127	likely benign	PTEN hamartoma tumor syndrome	2019-03-05	reviewed by expert panel	curation	PTEN c.-1195del12 (NC_000010.10:g.89623031_89623042delAAGCCGCAGCAA) 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). BS4_P: Lack of segregation in affected members of one family. (Internal laboratory contributor SCV SCV000222146.7) BP5: Variant found in multiple cases with alternate molecular basis for disease. (Internal laboratory contributors SCV000222146.7, SCV000183826.5)
Ambry Genetics	RCV000129113	SCV000183826	likely benign	Hereditary cancer-predisposing syndrome	2019-07-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
GeneDx	RCV000506666	SCV000222146	likely benign	not provided	2019-03-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21194675, 21956414, 25669429, 28821472, 28157521, 21532617)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000506666	SCV000602111	likely benign	not provided	2022-05-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000506666	SCV001148032	benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	KLLN: BS1, BS2; PTEN: BS1, BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV000790891	SCV003347311	uncertain significance	PTEN hamartoma tumor syndrome	2020-07-21	criteria provided, single submitter	clinical testing	This variant occurs in a non-coding region of the PTEN gene. It does not change the encoded amino acid sequence of the PTEN protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in individual(s) with clinical features of Cowden syndrome (PMID: 21194675, 21532617). This variant is also known as c.-1195del12 in the literature. ClinVar contains an entry for this variant (Variation ID: 189433). This variant has been reported to have conflicting or insufficient data to determine the effect on PTEN protein function (PMID: 21532617). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000129113	SCV004228122	likely benign	Hereditary cancer-predisposing syndrome	2023-09-12	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000506666	SCV005412166	uncertain significance	not provided	2023-10-11	criteria provided, single submitter	clinical testing