Submissions for variant NM_000051.4(ATM):c.4104_4105del (p.Ser1369fs)

dbSNP: rs879254189

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236151	SCV000293755	pathogenic	not provided	2023-10-07	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; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV000573604	SCV000672662	pathogenic	Hereditary cancer-predisposing syndrome	2016-06-16	criteria provided, single submitter	clinical testing	The c.4104_4105delTT pathogenic mutation, located in coding exon 26 of the ATM gene, results from a deletion of two nucleotides between nucleotide positions 4104 and 4105, 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).
Invitae	RCV000807392	SCV000947440	pathogenic	Ataxia-telangiectasia syndrome	2022-05-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1369Argfs*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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 246275). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000807392	SCV002511534	likely pathogenic	Ataxia-telangiectasia syndrome	2022-04-25	criteria provided, single submitter	clinical testing	Variant summary: ATM c.4104_4105delTT (p.Ser1369ArgfsX8) 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 248440 control chromosomes. To our knowledge, no occurrence of c.4104_4105delTT in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. Three 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/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Myriad Genetics, Inc.	RCV004020933	SCV004933785	pathogenic	Familial cancer of breast	2024-01-23	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics	RCV004020933	SCV005056957	likely pathogenic	Familial cancer of breast	2024-02-22	criteria provided, single submitter	clinical testing