Submissions for variant NM_000051.4(ATM):c.3626_3627del (p.Phe1209fs)

dbSNP: rs587782861

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000167290	SCV000218133	pathogenic	Hereditary cancer-predisposing syndrome	2023-06-12	criteria provided, single submitter	clinical testing	The c.3626_3627delTT pathogenic mutation, located in coding exon 24 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 3626 to 3627, causing a translational frameshift with a predicted alternate stop codon (p.F1209Yfs*19). 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	RCV000235460	SCV000293064	pathogenic	not provided	2023-06-09	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 significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 10330348, 10817650, 23807571, 25614872, 16461462, 28888541, 17124347)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000628123	SCV000749016	pathogenic	Ataxia-telangiectasia syndrome	2025-01-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe1209Tyrfs*19) 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 premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 10330348). ClinVar contains an entry for this variant (Variation ID: 187552). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000167290	SCV000911667	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 25 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. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000628123	SCV001338155	pathogenic	Ataxia-telangiectasia syndrome	2020-02-14	criteria provided, single submitter	clinical testing	Variant summary: ATM c.3626_3627delTT (p.Phe1209TyrfsX19) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251142 control chromosomes (gnomAD). c.3626_3627delTT has been reported in the literature in individuals affected with Ataxia-Telangiectasia (e.g. Teraoka_1999, Li_2000, Magliozzi_2006). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics	RCV003468804	SCV004212108	pathogenic	Familial cancer of breast	2023-01-19	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003468804	SCV004931206	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.
Fulgent Genetics, Fulgent Genetics	RCV005042345	SCV005681269	pathogenic	Familial cancer of breast; Ataxia-telangiectasia syndrome	2024-03-05	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000628123	SCV001457155	pathogenic	Ataxia-telangiectasia syndrome	2020-09-16	no assertion criteria provided	clinical testing
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	RCV001640248	SCV001852764	pathogenic	Ovarian carcinoma	2021-09-11	no assertion criteria provided	clinical testing