ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.553A>G (p.Ile185Val) (rs143962515)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000589048 SCV000884559 uncertain significance not provided 2017-10-20 criteria provided, single submitter clinical testing
ClinGen RASopathy Variant Curation Expert Panel RCV000520723 SCV000616524 benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.553A>G (p.Ile185Val) variant in the SOS1 gene is 0.087% (16/11574) of Latino chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000038564 SCV000857292 benign not specified 2017-10-24 criteria provided, single submitter clinical testing
GeneDx RCV000589048 SCV000209096 likely benign not provided 2016-03-01 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.
Illumina Clinical Services Laboratory,Illumina RCV000260347 SCV000430451 uncertain significance Gingival fibromatosis 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000319957 SCV000430452 uncertain significance Noonan syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589048 SCV000698642 benign not provided 2017-03-12 criteria provided, single submitter clinical testing Variant summary: The c.553G>A (p.Ile185Val) in SOS1 gene is a missense change that involves a non-conserved nucleotide and 5/5 in silico tools predict benign outcome. The variant is located outside of any known functional domain, however no functional studies confirming lack of impact of the variant on the protein function have been reported at the time of evaluation. The variant is present in the large control population datasets of ExAC and gnomAD at a frequency 0.0003395 and 0.0003576, respectively (41/120780 and 88/ 246106 chrs tested, respectively). These frequencies exceed the maximal expected frequency of a pathogenic allele (0.000035) in this gene. The variant has not, to our knowledge, been reported in affected individuals via published reports but cited as Likely Benign by a reputable databases/clinical laboratories. Taking together, the variant was classified as Benign.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038564 SCV000062242 uncertain significance not specified 2010-10-25 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ile185Val varia nt has not previously been reported in the literature or public databases, and i t has not been identified in our laboratory in more than 670 Caucasian probands. This variant was identified in a family member of this individual who is report edly unaffected with the clinical features of Noonan spectrum disorders. This po sition is not highly conserved in evolution, and the frog has a Val at this posi tion of the protein. Finally, this variant is predicted by three different compu tational tools to have a benign role, though it should be noted that the accurac y of these tools is not well understood. Therefore, while the clinical significa nce of this variant cannot be determined conclusively at this time, we lean towa rds it having a benign role.
PreventionGenetics RCV000038564 SCV000311205 likely benign not specified criteria provided, single submitter clinical testing

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