Submissions for variant NM_005591.4(MRE11):c.1447C>T (p.Arg483Ter)

gnomAD frequency: 0.00001  dbSNP: rs780001540

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000216978	SCV000275299	pathogenic	Hereditary cancer-predisposing syndrome	2023-05-19	criteria provided, single submitter	clinical testing	The p.R483* pathogenic mutation (also known as c.1447C>T), located in coding exon 12 of the MRE11A gene, results from a C to T substitution at nucleotide position 1447. This changes the amino acid from an arginine to a stop codon within coding exon 12. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000642442	SCV000764121	pathogenic	Ataxia-telangiectasia-like disorder	2023-03-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg483*) in the MRE11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MRE11 are known to be pathogenic (PMID: 23080121, 23912341). This variant is present in population databases (rs780001540, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. ClinVar contains an entry for this variant (Variation ID: 231449). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003469031	SCV004193785	likely pathogenic	Ataxia-telangiectasia-like disorder 1	2024-02-20	criteria provided, single submitter	clinical testing
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	RCV001554327	SCV001775542	pathogenic	Breast carcinoma	2021-08-10	no assertion criteria provided	clinical testing