Submissions for variant NM_000051.4(ATM):c.1321C>T (p.Gln441Ter)

dbSNP: rs1565382267

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000771731	SCV000904388	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 10 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM 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	RCV001223497	SCV001395649	pathogenic	Ataxia-telangiectasia syndrome	2024-01-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln441*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 627852). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000771731	SCV002694867	pathogenic	Hereditary cancer-predisposing syndrome	2020-02-25	criteria provided, single submitter	clinical testing	The p.Q441* pathogenic mutation (also known as c.1321C>T), located in coding exon 9 of the ATM gene, results from a C to T substitution at nucleotide position 1321. This changes the amino acid from a glutamine to a stop codon within coding exon 9. 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.
GeneDx	RCV003229860	SCV003927596	pathogenic	not provided	2022-11-23	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25614872, 23807571)
Myriad Genetics, Inc.	RCV004027238	SCV004933407	pathogenic	Familial cancer of breast	2024-01-16	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.