Submissions for variant NM_000051.4(ATM):c.3631del (p.Ala1211fs)

dbSNP: rs1064795885

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000485936	SCV000572107	likely pathogenic	not provided	2016-10-21	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in ATM is denoted c.3631delG at the cDNA level and p.Ala1211HisfsX4 (A1211HfsX4) at the protein level. The normal sequence, with the base that is deleted in braces, is TATG[G]CATC. The deletion causes a frameshift which changes an Alanine to a Histidine at codon 1211, and creates a premature stop codon at position 4 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. Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001251341	SCV001426905	likely pathogenic	Malignant tumor of breast	2020-07-10	criteria provided, single submitter	clinical testing	Variant summary: ATM c.3631delG (p.Ala1211HisfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251144 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3631delG in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Myriad Genetics, Inc.	RCV004023176	SCV004933725	pathogenic	Familial cancer of breast	2024-01-22	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.