Submissions for variant NM_005633.4(SOS1):c.743G>A (p.Arg248His)

dbSNP: rs775052125

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	RCV002308549	SCV002600410	uncertain significance	not specified	2022-10-10	criteria provided, single submitter	clinical testing	Variant summary: SOS1 c.743G>A (p.Arg248His) results in a non-conservative amino acid change located in the Dbl homology (DH) domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251212 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.743G>A 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.
Ambry Genetics	RCV004047719	SCV003528225	uncertain significance	Cardiovascular phenotype	2021-08-27	criteria provided, single submitter	clinical testing	The c.743G>A (p.R248H) alteration is located in exon 6 (coding exon 6) of the SOS1 gene. This alteration results from a G to A substitution at nucleotide position 743, causing the arginine (R) at amino acid position 248 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.