Submissions for variant NM_000051.4(ATM):c.1110C>G (p.Tyr370Ter)

dbSNP: rs376170600

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000131436	SCV000186418	pathogenic	Hereditary cancer-predisposing syndrome	2022-05-10	criteria provided, single submitter	clinical testing	The p.Y370* pathogenic mutation (also known as c.1110C>G), located in coding exon 8 of the ATM gene, results from a C to G substitution at nucleotide position 1110. This changes the amino acid from a tyrosine to a stop codon within coding exon 8. This amino acid position is not well conserved in available vertebrate species. In one study, this mutation was detected in conjunction with a second ATM mutation in two families with classic ataxia-telangiectasia (A-T) (Mitui M et al. Hum Mutat. 2003 Jul;22(1):43-50). In addition to the clinical data presented in the literature, 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228285	SCV000282861	pathogenic	Ataxia-telangiectasia syndrome	2023-09-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr370*) 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 premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 12815592, 15039971). ClinVar contains an entry for this variant (Variation ID: 142354).
GeneDx	RCV000236856	SCV000292937	pathogenic	not provided	2023-09-29	criteria provided, single submitter	clinical testing	Nonsense 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; Observed in individuals with breast cancer (Decker et al., 2017; Xie et al., 2017); Has been reported in trans with a pathogenic ATM variant in at least one individual with ataxia-telangiectasia (Mitui et al., 2003; Coutinho et al., 2004); This variant is associated with the following publications: (PMID: 25601159, 28580595, 28779002, 31589614, 25525159, 15039971, 12815592, 28152038, 28888541)
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000236856	SCV001447653	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131436	SCV001733906	pathogenic	Hereditary cancer-predisposing syndrome	2020-10-07	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 9 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in the compound heterozygous state in an individual affected with ataxia telangiectasia (PMID: 12815592, 15039971). 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.
AiLife Diagnostics, AiLife Diagnostics	RCV000236856	SCV002502146	pathogenic	not provided	2022-02-28	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000131436	SCV002529740	pathogenic	Hereditary cancer-predisposing syndrome	2021-09-09	criteria provided, single submitter	curation
Baylor Genetics	RCV003467175	SCV004209468	pathogenic	Familial cancer of breast	2024-03-14	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003467175	SCV004932669	pathogenic	Familial cancer of breast	2024-01-12	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Natera, Inc.	RCV000228285	SCV001456880	pathogenic	Ataxia-telangiectasia syndrome	2020-09-16	no assertion criteria provided	clinical testing