Submissions for variant NM_000051.4(ATM):c.3510dup (p.Gln1171fs)

dbSNP: rs876658899

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000222552	SCV000274734	pathogenic	Hereditary cancer-predisposing syndrome	2023-11-02	criteria provided, single submitter	clinical testing	The c.3510dupA pathogenic mutation, located in coding exon 23 of the ATM gene, results from a duplication of A at nucleotide position 3510, causing a translational frameshift with a predicted alternate stop codon (p.Q1171Tfs*8). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000462687	SCV000547023	pathogenic	Ataxia-telangiectasia syndrome	2024-01-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1171Thrfs*8) 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 0.003%). 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: 231011). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000222552	SCV001735735	pathogenic	Hereditary cancer-predisposing syndrome	2022-11-16	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 24 of the ATM gene, creating a frameshift and 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 1/251336 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.
Sema4, Sema4	RCV000222552	SCV002536079	likely pathogenic	Hereditary cancer-predisposing syndrome	2021-05-06	criteria provided, single submitter	curation
GeneDx	RCV002259324	SCV002538739	likely pathogenic	not provided	2022-06-27	criteria provided, single submitter	clinical testing	Frameshift 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; Not observed at a significant frequency in large population cohorts (gnomAD); Observed in an unaffected control (Lu 2019); This variant is associated with the following publications: (PMID: 29922827, 30128536)
Fulgent Genetics, Fulgent Genetics	RCV002500728	SCV002809914	likely pathogenic	Familial cancer of breast; Ataxia-telangiectasia syndrome	2022-01-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003469020	SCV004209420	pathogenic	Familial cancer of breast	2023-09-21	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003469020	SCV004933466	pathogenic	Familial cancer of breast	2024-01-22	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.