Submissions for variant NM_000051.4(ATM):c.4664del (p.Leu1555fs)

dbSNP: rs876659039

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000214193	SCV000275009	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-16	criteria provided, single submitter	clinical testing	The c.4664delT pathogenic mutation, located in coding exon 30 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 4664, causing a translational frameshift with a predicted alternate stop codon (p.L1555Pfs*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.
Counsyl	RCV000667950	SCV000792479	likely pathogenic	Ataxia-telangiectasia syndrome	2017-06-26	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000214193	SCV001350121	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 31 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000667950	SCV001395193	pathogenic	Ataxia-telangiectasia syndrome	2025-01-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu1555Profs*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 not present in population databases (gnomAD no frequency). 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: 231231). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV004020665	SCV004931350	pathogenic	Familial cancer of breast	2024-01-24	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.