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
Labcorp Genetics (formerly Invitae), Labcorp	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.