ClinVar Miner

Submissions for variant NM_000208.4(INSR):c.1550A>G (p.Glu517Gly)

gnomAD frequency: 0.00058  dbSNP: rs147671523
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001820051 SCV002066011 uncertain significance not specified 2019-04-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002486479 SCV002793181 uncertain significance Insulin-resistant diabetes mellitus AND acanthosis nigricans; Hyperinsulinism due to INSR deficiency; Leprechaunism syndrome; Rabson-Mendenhall syndrome 2022-04-05 criteria provided, single submitter clinical testing
Invitae RCV001355872 SCV003289773 benign not provided 2022-06-11 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003946018 SCV004763471 likely benign INSR-related condition 2023-04-04 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001355872 SCV001550884 uncertain significance not provided no assertion criteria provided clinical testing The INSR p.Glu517Gly variant was not identified in the literature nor was it identified in ClinVar, Cosmic, or LOVD 3.0. The variant was identified in dbSNP (ID: rs147671523) and in control databases in 45 of 282816 chromosomes at a frequency of 0.000159 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 38 of 24942 chromosomes (freq: 0.001524), Latino in 6 of 35438 chromosomes (freq: 0.000169) and South Asian in 1 of 30616 chromosomes (freq: 0.000033); it was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), and Other populations. The p.Glu517 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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