ClinVar Miner

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

gnomAD frequency: 0.00047  dbSNP: rs745857330
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000726299 SCV000343527 uncertain significance not provided 2017-05-17 criteria provided, single submitter clinical testing
Illumina Laboratory Services, 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 Laboratory Services, Illumina RCV000308234 SCV000415584 uncertain significance Rabson-Mendenhall 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 Laboratory Services, 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
Invitae RCV000726299 SCV002268999 benign not provided 2024-01-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002518075 SCV003692446 uncertain significance Inborn genetic diseases 2022-09-14 criteria provided, single submitter clinical testing The c.41T>C (p.L14P) alteration is located in exon 1 (coding exon 1) of the INSR gene. This alteration results from a T to C substitution at nucleotide position 41, causing the leucine (L) at amino acid position 14 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.