Submissions for variant NM_000051.4(ATM):c.3596A>G (p.Glu1199Gly)

dbSNP: rs876660855

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000214172	SCV000278616	uncertain significance	Hereditary cancer-predisposing syndrome	2021-10-08	criteria provided, single submitter	clinical testing	The p.E1199G variant (also known as c.3596A>G), located in coding exon 24 of the ATM gene, results from an A to G substitution at nucleotide position 3596. The glutamic acid at codon 1199 is replaced by glycine, an amino acid with similar properties. This amino acid position is not 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	RCV000471935	SCV000546838	uncertain significance	Ataxia-telangiectasia syndrome	2023-11-18	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1199 of the ATM protein (p.Glu1199Gly). 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: 234109). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Color Diagnostics, LLC DBA Color Health	RCV000214172	SCV000906479	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glycine at codon 1199 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 reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. 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.
GeneDx	RCV001577594	SCV001804997	uncertain significance	not provided	2021-06-29	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Fulgent Genetics, Fulgent Genetics	RCV002485435	SCV002782899	uncertain significance	Familial cancer of breast; Ataxia-telangiectasia syndrome	2021-10-25	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000471935	SCV002082855	uncertain significance	Ataxia-telangiectasia syndrome	2021-03-12	no assertion criteria provided	clinical testing