ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2276G>A (p.Ser759Asn)

dbSNP: rs786202270
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164999 SCV000215693 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-14 criteria provided, single submitter clinical testing The p.S759N variant (also known as c.2276G>A), located in coding exon 14 of the ATM gene, results from a G to A substitution at nucleotide position 2276. The serine at codon 759 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been detected in 1/4112 breast cancer patients and 0/2399 healthy control individuals across numerous studies (Tavtigian S et al. Am J Hum Genet. 2009 Oct;85(4):427-46). Additionally, this alteration was observed in a study of 1010 unrelated Indian patients with breast and/or ovarian cancer (Singh J et al. Breast Cancer Res Treat, 2018 Jul;170:189-196). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000474605 SCV000546824 uncertain significance Ataxia-telangiectasia syndrome 2022-09-09 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 759 of the ATM protein (p.Ser759Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 19781682, 29470806). ClinVar contains an entry for this variant (Variation ID: 185556). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000521181 SCV000617366 uncertain significance not provided 2023-08-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in individuals with breast cancer without detailed clinical information provided (Tavtigian et al., 2009; Broeks et al., 2008); This variant is associated with the following publications: (PMID: 17393301, 29470806, 19781682)
Color Diagnostics, LLC DBA Color Health RCV000164999 SCV000687373 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-05 criteria provided, single submitter clinical testing This missense variant replaces serine with asparagine at codon 759 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 19781682). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Counsyl RCV000474605 SCV000792219 uncertain significance Ataxia-telangiectasia syndrome 2017-06-19 criteria provided, single submitter clinical testing
Baylor Genetics RCV003468727 SCV004207068 uncertain significance Familial cancer of breast 2023-10-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV000474605 SCV001462059 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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