Submissions for variant NM_005633.4(SOS1):c.3391+5G>C

dbSNP: rs1668654438

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001280998	SCV001468394	uncertain significance	Fibromatosis, gingival, 1; Noonan syndrome 4	2021-03-30	criteria provided, single submitter	clinical testing	SOS1 NM_005633.3 exon 21 c.3391+5G>C: This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Splice prediction tools suggest that this variant may affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003655334	SCV004552061	uncertain significance	RASopathy	2023-09-25	criteria provided, single submitter	clinical testing	This sequence change falls in intron 21 of the SOS1 gene. It does not directly change the encoded amino acid sequence of the SOS1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 992530). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.