Submissions for variant NM_000051.4(ATM):c.2727del (p.Thr910fs)

dbSNP: rs1555083267

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657392	SCV000779125	pathogenic	not provided	2017-10-11	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in ATM is denoted c.2727delT at the cDNA level and p.Thr910LeufsX19 (T910LfsX19) at the protein level. The normal sequence, with the base that is deleted in brackets, is TAAC[delT]ACTG. The deletion causes a frameshift which changes a Threonine to a Leucine at codon 910, and creates a premature stop codon at position 19 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000687447	SCV000815012	pathogenic	Ataxia-telangiectasia syndrome	2022-10-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr910Leufs*19) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). ClinVar contains an entry for this variant (Variation ID: 545827).
Myriad Genetics, Inc.	RCV004026003	SCV004932517	pathogenic	Familial cancer of breast	2024-01-18	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.