Submissions for variant NM_000051.4(ATM):c.1367del (p.Leu456fs)

dbSNP: rs1555070832

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657487	SCV000779222	likely pathogenic	not provided	2018-03-08	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in ATM is denoted c.1367delT at the cDNA level and p.Leu456TyrfsX17 (L456YfsX17) at the protein level. The normal sequence, with the base that is deleted in brackets, is GTGT[delT]ACGA. The deletion causes a frameshift which changes a Leucine to a Tyrosine at codon 456, and creates a premature stop codon at position 17 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature as a germline variant, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider ATM c.1367delT to be a likely pathogenic variant.
Genetic Services Laboratory, University of Chicago	RCV000657487	SCV002064368	pathogenic	not provided	2020-06-03	criteria provided, single submitter	clinical testing	DNA sequence analysis of the ATM gene demonstrated a single base pair deletion in exon 10, c.1367del. This pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 16 amino acids downstream of the mutation, p.Leu456Tyrfs*17. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated ATM protein with potentially abnormal function. This sequence change is absent from known population databases (gnomAD). This sequence change has not been previously described in patients with ATM-related disorders; however, other truncating variants have been described in this gene. These collective evidences indicate that this sequence change is pathogenic.
Myriad Genetics, Inc.	RCV004026008	SCV004932631	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.
Baylor Genetics	RCV004026008	SCV005053013	likely pathogenic	Familial cancer of breast	2023-11-22	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001829818	SCV002095289	likely pathogenic	Ataxia-telangiectasia syndrome	2020-07-09	no assertion criteria provided	clinical testing