Submissions for variant NM_005633.4(SOS1):c.899G>A (p.Arg300Gln)

gnomAD frequency: 0.00002  dbSNP: rs754374236

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000800167	SCV001192881	likely benign	RASopathy	2019-12-05	reviewed by expert panel	curation	The c.899G>A (p.Arg300Gln) variant in SOS1 is present in 0.01% (3/30610) South Asian alleles in gnomAD. Computational prediction tools and conservation analysis suggest that this variant does not impact the protein (BP4). This variant has been identified in 5 probands with an alternate molecular basis for disease (BP5: SCV000430444.2; SCV000430443.2; SCV000730061.1; SCV000939867.1). In summary, the clinical significance of the p.Arg300Gln variant is likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP4, BP5.
Illumina Laboratory Services, Illumina	RCV000307592	SCV000430443	uncertain significance	Fibromatosis, gingival, 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000362251	SCV000430444	uncertain significance	Noonan syndrome 4	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000606984	SCV000730061	likely benign	not specified	2018-02-15	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000800167	SCV000939867	likely benign	RASopathy	2022-08-04	criteria provided, single submitter	clinical testing