Submissions for variant NM_000051.4(ATM):c.1920_1923del (p.Glu641fs)

dbSNP: rs1555073111

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000572580	SCV000665483	pathogenic	Hereditary cancer-predisposing syndrome	2016-02-02	criteria provided, single submitter	clinical testing	The c.1920_1923delAGAA pathogenic mutation, located in coding exon 12 of the ATM gene, results from a deletion of 4 nucleotides between nucleotide positions 1920 and 1923, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000627896	SCV000748780	pathogenic	Ataxia-telangiectasia syndrome	2017-11-16	criteria provided, single submitter	clinical testing	Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant has not been reported in the literature in individuals with ATM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu641Asnfs*7) in the ATM gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000572580	SCV000913113	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 4 nucleotides in exon 13 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.
Baylor Genetics	RCV003459315	SCV004213925	likely pathogenic	Familial cancer of breast	2022-02-17	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003459315	SCV004933797	pathogenic	Familial cancer of breast	2024-01-16	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.