Submissions for variant NM_000051.4(ATM):c.1651G>T (p.Val551Phe)

dbSNP: rs1555071742

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589833	SCV000694191	uncertain significance	not provided	2017-01-03	criteria provided, single submitter	clinical testing	Variant summary: The ATM c.1651G>T (p.Val551Phe) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121354 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Ambry Genetics	RCV001012576	SCV001173045	uncertain significance	Hereditary cancer-predisposing syndrome	2024-02-13	criteria provided, single submitter	clinical testing	The p.V551F variant (also known as c.1651G>T), located in coding exon 10 of the ATM gene, results from a G to T substitution at nucleotide position 1651. The valine at codon 551 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is not 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	RCV001853968	SCV002261918	uncertain significance	Ataxia-telangiectasia syndrome	2021-09-07	criteria provided, single submitter	clinical testing	This sequence change replaces valine with phenylalanine at codon 551 of the ATM protein (p.Val551Phe). The valine residue is moderately conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency). 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: 495386). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM 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.
Baylor Genetics	RCV003459451	SCV004215516	uncertain significance	Familial cancer of breast	2023-05-22	criteria provided, single submitter	clinical testing