Submissions for variant NM_000051.4(ATM):c.1305del (p.Leu435fs)

dbSNP: rs1555070719

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000674459	SCV000799798	likely pathogenic	Ataxia-telangiectasia syndrome	2018-05-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000674459	SCV001591591	pathogenic	Ataxia-telangiectasia syndrome	2020-05-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu435Phefs*2) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 558225). This variant is not present in population databases (ExAC no frequency). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002386151	SCV002689938	pathogenic	Hereditary cancer-predisposing syndrome	2024-12-22	criteria provided, single submitter	clinical testing	The c.1305delA pathogenic mutation, located in coding exon 9 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 1305, causing a translational frameshift with a predicted alternate stop codon (p.L435Ffs*2). 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.
Myriad Genetics, Inc.	RCV004026135	SCV004933661	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.