Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000589437 | SCV000344629 | uncertain significance | not provided | 2016-09-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589437 | SCV000698619 | uncertain significance | not provided | 2016-05-23 | criteria provided, single submitter | clinical testing | Variant summary: The SOS1 c.1820T>C (p.Ile607Thr) variant causes a missense change involving a highly conserved nucleotide with 2/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a benign outcome, although these predictions have yet to be functionally assessed. This variant was observed in the large, broad control population, ExAC, with an allele frequency of 2/120916 (1/60458, frequency: 0.0000165), which does not exceed the estimated maximal expected allele frequency for a pathogenic SOS1 variant of 1/33333(0.00003) but does not rule out a possibility for it to be a rare functional polymorphism. The fact that c.1820T>C co-occurred with a known pathogenic variant in PTPN1 gene suggest a non-contributory role of the variant of interest. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Due to the absence of clinical information and lack of functional studies, the variant has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. |
Labcorp Genetics |
RCV001240108 | SCV001413031 | likely benign | RASopathy | 2023-02-06 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002467722 | SCV002763372 | uncertain significance | Noonan syndrome 4 | criteria provided, single submitter | clinical testing | ||
Genome- |
RCV002467721 | SCV002763373 | uncertain significance | Fibromatosis, gingival, 1 | criteria provided, single submitter | clinical testing | ||
Ambry Genetics | RCV004992164 | SCV005506082 | uncertain significance | Cardiovascular phenotype | 2024-07-10 | criteria provided, single submitter | clinical testing | The p.I607T variant (also known as c.1820T>C), located in coding exon 10 of the SOS1 gene, results from a T to C substitution at nucleotide position 1820. The isoleucine at codon 607 is replaced by threonine, an amino acid with similar properties. This variant has been detected in a prenatal specimen with cystic hygroma, increased nuchal translucency, and congenital heart defect (Leach NT et al. Genet Med, 2019 Feb;21:417-425). This variant co-occurred with a second SOS1 variant in two members of a family with dilated cardiomyopathy; however, both variants were absent in one affected family member (Cowan JR et al. Circ Genom Precis Med, 2020 Aug;13:e002892). Functional studies suggest this variant may impact ERK expression; however, additional evidence is needed to confirm this finding (Cowan JR et al. Circ Genom Precis Med, 2020 Aug;13:e002892). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
University of Washington Center for Mendelian Genomics, |
RCV001543366 | SCV001761924 | uncertain significance | Primary dilated cardiomyopathy | no assertion criteria provided | research |