Submissions for variant NM_006939.4(SOS2):c.1564ATA[1] (p.Ile523del)

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	RCV002283381	SCV002571876	uncertain significance	not specified	2022-08-01	criteria provided, single submitter	clinical testing	Variant summary: SOS2 c.1567_1569delATA (p.Ile523del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 8e-06 in 251206 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1567_1569delATA in individuals affected with Noonan Syndrome 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 uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003096360	SCV003290570	uncertain significance	Noonan syndrome 9	2024-03-23	criteria provided, single submitter	clinical testing	This variant, c.1567_1569del, results in the deletion of 1 amino acid(s) of the SOS2 protein (p.Ile523del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs748120062, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.