Submissions for variant NM_000051.4(ATM):c.3614G>A (p.Arg1205His)

gnomAD frequency: 0.00006  dbSNP: rs769106895

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000227875	SCV000282935	uncertain significance	Ataxia-telangiectasia syndrome	2023-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1205 of the ATM protein (p.Arg1205His). This variant is present in population databases (rs769106895, gnomAD 0.01%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 30287823, 31159747). ClinVar contains an entry for this variant (Variation ID: 236707). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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	RCV000486877	SCV000569511	uncertain significance	not provided	2023-11-30	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32566746, 36243179, 19781682, 31159747, 30287823)
Ambry Genetics	RCV000569109	SCV000665259	likely benign	Hereditary cancer-predisposing syndrome	2018-04-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneKor MSA	RCV000569109	SCV000821850	uncertain significance	Hereditary cancer-predisposing syndrome	2018-08-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000569109	SCV000903866	likely benign	Hereditary cancer-predisposing syndrome	2016-04-08	criteria provided, single submitter	clinical testing
Cancer Genomics Group, Japanese Foundation For Cancer Research	RCV001030527	SCV001193475	uncertain significance	Hereditary breast ovarian cancer syndrome	2019-05-01	criteria provided, single submitter	research
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000486877	SCV002010823	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001818551	SCV002064590	uncertain significance	not specified	2019-06-08	criteria provided, single submitter	clinical testing