Submissions for variant NM_000051.4(ATM):c.6343G>C (p.Val2115Leu)

dbSNP: rs587780634

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000476158	SCV000546667	uncertain significance	Ataxia-telangiectasia syndrome	2024-01-02	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2115 of the ATM protein (p.Val2115Leu). This variant is present in population databases (rs587780634, gnomAD 0.02%). 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: 407461). 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	RCV000581801	SCV000687688	uncertain significance	Hereditary cancer-predisposing syndrome	2020-12-07	criteria provided, single submitter	clinical testing	This missense variant replaces valine with leucine at codon 2115 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 5/249350 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.
Ambry Genetics	RCV000581801	SCV002659525	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-13	criteria provided, single submitter	clinical testing	The c.6343G>C (p.V2115L) alteration is located in exon 43 (coding exon 42) of the ATM gene. This alteration results from a G to C substitution at nucleotide position 6343, causing the valine (V) at amino acid position 2115 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003493576	SCV004243454	uncertain significance	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000476158	SCV001452120	uncertain significance	Ataxia-telangiectasia syndrome	2020-01-24	no assertion criteria provided	clinical testing