Submissions for variant NM_000051.4(ATM):c.9070A>C (p.Thr3024Pro)

dbSNP: rs587781630

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129735	SCV000184541	uncertain significance	Hereditary cancer-predisposing syndrome	2022-12-05	criteria provided, single submitter	clinical testing	The p.T3024P variant (also known as c.9070A>C), located in coding exon 62 of the ATM gene, results from an A to C substitution at nucleotide position 9070. The threonine at codon 3024 is replaced by proline, an amino acid with highly similar properties. 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	RCV000230735	SCV000283105	uncertain significance	Ataxia-telangiectasia syndrome	2023-12-01	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 3024 of the ATM protein (p.Thr3024Pro). This variant is present in population databases (rs587781630, gnomAD 0.0009%). This missense change has been observed in individual(s) with breast cancer (PMID: 34326862). ClinVar contains an entry for this variant (Variation ID: 141284). 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 disruptive. 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	RCV000129735	SCV000687877	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with proline at codon 3024 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 been identified in 2/251458 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.
GeneDx	RCV001578023	SCV001805539	uncertain significance	not provided	2022-10-12	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (gnomAD); Observed in an unaffected individual in a case-control study (Tiao et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28652578, 23532176)
Sema4, Sema4	RCV000129735	SCV002530714	uncertain significance	Hereditary cancer-predisposing syndrome	2021-10-30	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002478390	SCV002792280	uncertain significance	Familial cancer of breast; Ataxia-telangiectasia syndrome	2021-10-26	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV004567095	SCV005057119	uncertain significance	Familial cancer of breast	2023-12-27	criteria provided, single submitter	clinical testing