Submissions for variant NM_000455.5(STK11):c.921-9C>T

gnomAD frequency: 0.00001  dbSNP: rs761688641

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000990132	SCV000253268	likely benign	Peutz-Jeghers syndrome	2024-01-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000679329	SCV000602243	likely benign	not provided	2022-10-05	criteria provided, single submitter	clinical testing	To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000081 (2/24694 chromosomes, http://gnomad.broadinstitute.org), is uninformative in 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 STK11 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.
Color Diagnostics, LLC DBA Color Health	RCV000580751	SCV000686706	likely benign	Hereditary cancer-predisposing syndrome	2017-06-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000679329	SCV000806095	likely benign	not provided	2017-06-20	criteria provided, single submitter	clinical testing
Mendelics	RCV000990132	SCV001140944	likely benign	Peutz-Jeghers syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000507064	SCV001482087	uncertain significance	not specified	2021-02-12	criteria provided, single submitter	clinical testing	Variant summary: STK11 c.921-9C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 3/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.6e-05 in 153524 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.921-9C>T in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=1) and likely benign (n=4). Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx	RCV000679329	SCV001895453	likely benign	not provided	2019-11-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000990132	SCV002057320	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000580751	SCV002526961	likely benign	Hereditary cancer-predisposing syndrome	2021-07-20	criteria provided, single submitter	curation