Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV001820051 | SCV002066011 | uncertain significance | not specified | 2019-04-05 | criteria provided, single submitter | clinical testing | |
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 | |
Prevention |
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, |
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. |