Submissions for variant NM_007194.4(CHEK2):c.1164dup (p.Thr389fs)

dbSNP: rs758677815

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000464286	SCV000550433	pathogenic	Familial cancer of breast	2021-07-14	criteria provided, single submitter	clinical testing	This sequence change inserts 1 nucleotide in exon 11 of the CHEK2 mRNA (c.1164dupC), causing a frameshift at codon 389. This creates a premature translational stop signal (p.Thr389Hisfs*6) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV000464286	SCV004044233	pathogenic	Familial cancer of breast	2023-06-28	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Color Diagnostics, LLC DBA Color Health	RCV003584611	SCV004361357	pathogenic	Hereditary cancer-predisposing syndrome	2022-12-05	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 11 of the CHEK2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with CHEK2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CHEK2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.