Submissions for variant NM_000051.4(ATM):c.5892G>C (p.Lys1964Asn)

gnomAD frequency: 0.00001  dbSNP: rs786202728

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165684	SCV000216422	uncertain significance	Hereditary cancer-predisposing syndrome	2022-01-27	criteria provided, single submitter	clinical testing	The c.5892G>C (p.K1964N) alteration is located in exon 39 (coding exon 38) of the ATM gene. This alteration results from a G to C substitution at nucleotide position 5892, causing the lysine (K) at amino acid position 1964 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000628179	SCV000749072	uncertain significance	Ataxia-telangiectasia syndrome	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1964 of the ATM protein (p.Lys1964Asn). This variant is present in population databases (rs786202728, gnomAD 0.0009%). 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: 186146). 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	RCV000165684	SCV001352372	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-06	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with asparagine at codon 1964 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 been reported in an individual affected with breast cancer (PMID: 35402282). This variant has been identified in 1/250968 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.
Athena Diagnostics	RCV000844955	SCV002771821	uncertain significance	not provided	2022-03-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000844955	SCV004035618	uncertain significance	not provided	2023-09-14	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; Observed in an individual with breast cancer (Abdel-Razeq et al., 2022); This variant is associated with the following publications: (PMID: 35402282, 23532176)
Baylor Genetics	RCV004567279	SCV005056929	uncertain significance	Familial cancer of breast	2024-02-29	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000844955	SCV000986780	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 03/23/2018 by GTR ID Credit Valley Hospital Department of Laboratory Medicine. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Natera, Inc.	RCV000628179	SCV001452331	uncertain significance	Ataxia-telangiectasia syndrome	2020-09-16	no assertion criteria provided	clinical testing