ClinVar Miner

Submissions for variant NM_000208.4(INSR):c.3143G>A (p.Gly1048Asp)

gnomAD frequency: 0.00005  dbSNP: rs200921389
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778147 SCV000914278 uncertain significance Insulin-resistant diabetes mellitus AND acanthosis nigricans 2019-04-05 criteria provided, single submitter clinical testing The INSR c.3143G>A (p.Gly1048Asp) missense variant has been reported in one study in which it was found in two affected siblings in a compound heterozygous state with a second missense variant (Ogawa et al. 2009). Both were noted to have acanthosis nigricans, hirsutism, prominent facial acne and impaired glucose tolerance. Control data are unavailable for the p.Gly1048Asp variant which is reported at a frequency of 0.001113 in the East Asian population of the Genome Aggregation Database. Phosphorylation of insulin receptors in erythrocytes from the siblings was not affected by insulin stimulation, unlike in control subjects where receptor phosphorylation was increased by insulin (Ogawa et al. 2009). The evidence for this variant is limited. The p.Gly1048Asp variant is therefore classified as a variant of uncertain significance but suspicious for diabetes mellitus, insulin-resistance, with acanthosis nigricans. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Illumina Laboratory Services, Illumina RCV001132181 SCV001291835 uncertain significance Leprechaunism syndrome 2017-05-02 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001132182 SCV001291836 uncertain significance Rabson-Mendenhall syndrome 2017-05-02 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Fulgent Genetics, Fulgent Genetics RCV002487597 SCV002791053 uncertain significance Insulin-resistant diabetes mellitus AND acanthosis nigricans; Hyperinsulinism due to INSR deficiency; Leprechaunism syndrome; Rabson-Mendenhall syndrome 2022-03-05 criteria provided, single submitter clinical testing

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