Submissions for variant NM_000051.4(ATM):c.4106C>A (p.Ser1369Ter)

gnomAD frequency: 0.00001  dbSNP: rs1057520640

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000435435	SCV000516711	pathogenic	not provided	2015-04-14	criteria provided, single submitter	clinical testing	This pathogenic variant is denoted ATM c.4106C>A at the cDNA level and p.Ser1369Ter (S1369X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic. The presence of
Invitae	RCV000472677	SCV000546927	pathogenic	Ataxia-telangiectasia syndrome	2023-11-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1369*) 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 present in population databases (no rsID available, gnomAD 0.0009%). 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: 379550). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000565000	SCV000660627	pathogenic	Hereditary cancer-predisposing syndrome	2023-03-29	criteria provided, single submitter	clinical testing	The p.S1369* pathogenic mutation (also known as c.4106C>A), located in coding exon 26 of the ATM gene, results from a C to A substitution at nucleotide position 4106. This changes the amino acid from a serine to a stop codon within coding exon 26. 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.
Counsyl	RCV000472677	SCV000678102	likely pathogenic	Ataxia-telangiectasia syndrome	2017-05-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000565000	SCV001736199	pathogenic	Hereditary cancer-predisposing syndrome	2021-01-11	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 27 of the ATM gene, creating a 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 hereditary cancer in the literature. This variant has been identified in 1/31384 chromosomes 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.
Fulgent Genetics, Fulgent Genetics	RCV002506024	SCV002797827	pathogenic	Familial cancer of breast; Ataxia-telangiectasia syndrome	2022-04-12	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003470377	SCV004207094	pathogenic	Familial cancer of breast	2023-09-30	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003470377	SCV004933860	pathogenic	Familial cancer of breast	2024-01-23	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.