ClinVar Miner

Submissions for variant NM_000875.5(IGF1R):c.1862C>T (p.Ser621Leu) (rs1131691583)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493390 SCV000582423 likely pathogenic not provided 2015-09-10 criteria provided, single submitter clinical testing The S621L variant in the IGF1R gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The S621L variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S621L variant is a non-conservative amino acid substitution, which occurs within the Fibronectin type-III 2 domain at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (V629E) has been reported in the Human Gene Mutation Database in association with intrauterine and postnatal growth retardation (Stenson et al., 2014), supporting the functional importance of this region of the protein. The S621L variant is a strong candidate for a disease-causing variant. However the possibility it may be a rare benign variant cannot be excluded.
GenomeConnect, ClinGen RCV000844968 SCV000986793 not provided IGF1R-Related Disorder no assertion provided phenotyping only Variant interpretted as Likely pathogenic and reported on 09/17/2015 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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