ClinVar Miner

Submissions for variant NM_000208.4(INSR):c.41T>C (p.Leu14Pro) (rs745857330)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726299 SCV000343527 uncertain significance not provided 2017-05-17 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000408260 SCV000415583 uncertain significance Insulin-resistant diabetes mellitus AND acanthosis nigricans 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000308234 SCV000415584 uncertain significance Pineal hyperplasia AND diabetes mellitus syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000365243 SCV000415585 uncertain significance Leprechaunism syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000726299 SCV000566427 uncertain significance not provided 2017-02-21 criteria provided, single submitter clinical testing The L14P variant in the INSR gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L14P variant is not observed at a significant frequency in large population cohorts; however, limited data are available (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L14P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L14P as a variant of uncertain significance.
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV000664158 SCV000787610 uncertain significance Monogenic diabetes 2018-04-09 criteria provided, single submitter research ACMG criteria: PP3 (4 predictors), BP4 (5 predictors), called VUS in ClinVar by Illumina, Emory and GeneDx, (PM1) residue 14 is within the signal peptide (PMIDs: 8257688, 2983222, 2211730), REVEL 0.52=VUS

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