Submissions for variant NM_000051.4(ATM):c.3935dup (p.Glu1313fs)

dbSNP: rs876659672

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000223199	SCV000276377	pathogenic	Hereditary cancer-predisposing syndrome	2021-09-13	criteria provided, single submitter	clinical testing	The c.3935dupG pathogenic mutation, located in coding exon 25 of the ATM gene, results from a duplication of one nucleotide at position 3935, causing a translational frameshift with a predicted alternate stop codon (p.E1313Rfs*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	RCV000411978	SCV000485622	likely pathogenic	Ataxia-telangiectasia syndrome	2016-01-18	criteria provided, single submitter	clinical testing
Invitae	RCV000411978	SCV000547131	pathogenic	Ataxia-telangiectasia syndrome	2023-12-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1313Argfs*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: 232284). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000483621	SCV000572793	pathogenic	not provided	2022-10-24	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); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene referred for genetic testing at GeneDx; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 27449771)
Baylor Genetics	RCV003462490	SCV004207060	likely pathogenic	Familial cancer of breast	2023-10-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000223199	SCV004360028	pathogenic	Hereditary cancer-predisposing syndrome	2022-07-26	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 26 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. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.
Myriad Genetics, Inc.	RCV003462490	SCV004931594	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.