Submissions for variant NM_015311.3(OBSL1):c.3603_3618del (p.Pro1203fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002510411	SCV002819720	likely pathogenic	3M syndrome 2	2022-12-21	criteria provided, single submitter	clinical testing	Variant summary: OBSL1 c.3603_3618del16 (p.Pro1203ThrfsX12) 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 associated with 3-M syndrome and Myopathy in HGMD. The variant was absent in 240458 control chromosomes. To our knowledge, no occurrence of c.3603_3618del16 in individuals affected with Three M Syndrome 2 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003561057	SCV004306735	uncertain significance	not provided	2023-12-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro1203Thrfs*12) in the OBSL1 gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with OBSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1878358). 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.