Submissions for variant NM_007194.4(CHEK2):c.1072C>T (p.Gln358Ter)

dbSNP: rs878854909

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000229454	SCV000289642	pathogenic	Familial cancer of breast	2023-06-15	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 240727). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln358*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400).
Ambry Genetics	RCV000568332	SCV000666355	pathogenic	Hereditary cancer-predisposing syndrome	2022-10-20	criteria provided, single submitter	clinical testing	The p.Q358* pathogenic mutation (also known as c.1072C>T), located in coding exon 9 of the CHEK2 gene, results from a C to T substitution at nucleotide position 1072. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV000229454	SCV004043600	pathogenic	Familial cancer of breast	2023-06-27	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001795369	SCV002035014	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001795369	SCV002037520	pathogenic	not provided		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000229454	SCV002588974	pathogenic	Familial cancer of breast	2022-08-26	no assertion criteria provided	clinical testing