Submissions for variant NM_000051.4(ATM):c.5156A>G (p.Asn1719Ser)

dbSNP: rs183531638

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000485988	SCV000570484	uncertain significance	not provided	2021-12-01	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 26933808)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000546123	SCV000622568	uncertain significance	Ataxia-telangiectasia syndrome	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1719 of the ATM protein (p.Asn1719Ser). This variant is present in population databases (rs183531638, gnomAD 0.003%). 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: 421320). 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.
Ambry Genetics	RCV000565111	SCV000660601	likely benign	Hereditary cancer-predisposing syndrome	2023-10-03	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.
Color Diagnostics, LLC DBA Color Health	RCV000565111	SCV000682252	uncertain significance	Hereditary cancer-predisposing syndrome	2022-08-08	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with serine at codon 1719 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 hereditary cancer in the literature. This variant has been identified in 1/251046 chromosomes 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.
AiLife Diagnostics, AiLife Diagnostics	RCV000485988	SCV002503330	uncertain significance	not provided	2020-05-13	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000565111	SCV002527867	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-31	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002481518	SCV002784375	uncertain significance	Familial cancer of breast; Ataxia-telangiectasia syndrome	2022-05-13	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003470569	SCV004209396	uncertain significance	Familial cancer of breast	2024-02-20	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000546123	SCV002080839	uncertain significance	Ataxia-telangiectasia syndrome	2020-01-22	no assertion criteria provided	clinical testing