Submissions for variant NM_007194.4(CHEK2):c.100C>T (p.Gln34Ter)

dbSNP: rs1231012263

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000584578	SCV000689625	pathogenic	Hereditary cancer-predisposing syndrome	2023-08-28	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 2 of the CHEK2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast cancer (PMID: 33925588, ClinVar SCV000914197.1). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000778091	SCV000961633	pathogenic	Familial cancer of breast	2024-02-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln34*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 491586). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000584578	SCV001177992	pathogenic	Hereditary cancer-predisposing syndrome	2022-04-28	criteria provided, single submitter	clinical testing	The p.Q34* pathogenic mutation (also known as c.100C>T), located in coding exon 1 of the CHEK2 gene, results from a C to T substitution at nucleotide position 100. This changes the amino acid from a glutamine to a stop codon within coding exon 1. 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.	RCV000778091	SCV004043684	pathogenic	Familial cancer of breast	2023-06-22	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.
Fulgent Genetics, Fulgent Genetics	RCV005034151	SCV005663149	likely pathogenic	Li-Fraumeni syndrome 2; Bone osteosarcoma; Familial prostate cancer	2024-04-29	criteria provided, single submitter	clinical testing
Academic Center for Education, Culture and Research, Motamed Cancer Institute	RCV000778091	SCV000914197	pathogenic	Familial cancer of breast	2019-05-21	no assertion criteria provided	clinical testing