Submissions for variant NM_000051.4(ATM):c.649_651dup (p.Ile217dup)

dbSNP: rs1565369864

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000774191	SCV000907892	uncertain significance	Hereditary cancer-predisposing syndrome	2019-06-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000774191	SCV001187498	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-22	criteria provided, single submitter	clinical testing	The c.649_651dupATT variant (also known as p.I217dup), located in coding exon 5 of the ATM gene, results from an in-frame duplication of ATT at nucleotide positions 649 to 651. This results in the duplication of an extra isoleucine residue between codons 217 and 218. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001051655	SCV001215823	uncertain significance	Ataxia-telangiectasia syndrome	2023-05-24	criteria provided, single submitter	clinical testing	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. This variant, c.649_651dup, results in the insertion of 1 amino acid(s) of the ATM protein (p.Ile217dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD 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: 629484). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown.
Fulgent Genetics, Fulgent Genetics	RCV002487584	SCV002797153	uncertain significance	Familial cancer of breast; Ataxia-telangiectasia syndrome	2021-07-26	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150346	SCV003838933	uncertain significance	Breast and/or ovarian cancer	2021-11-24	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001796208	SCV002034322	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001796208	SCV002035259	uncertain significance	not provided		no assertion criteria provided	clinical testing