Submissions for variant NM_005633.4(SOS1):c.511-5T>C

gnomAD frequency: 0.00001  dbSNP: rs1558491271

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	RCV001192790	SCV001361135	uncertain significance	not specified	2019-06-03	criteria provided, single submitter	clinical testing	Variant summary: SOS1 c.511-5T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 248702 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.511-5T>C in individuals affected with Noonan Syndrome and Related Conditions 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.
Invitae	RCV001428249	SCV001630945	likely benign	RASopathy	2023-05-26	criteria provided, single submitter	clinical testing