ClinVar Miner

Submissions for variant NM_000618.5(IGF1):c.274G>A (p.Val92Met)

dbSNP: rs121912430
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002264908 SCV002546685 likely pathogenic not provided 2023-10-12 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: reduced binding affinity of IGF1 to the IGF1-receptor with reduced IGF1-receptor autophosphorylation/activation (Walenkamp et al., 2005; Denley et al., 2005); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as V44M; This variant is associated with the following publications: (PMID: 25680077, 26034074, 29311900, 31416218, 21845174, 28149264, 31456057, 31736316, 22587301, 23392101, 22654835, 17785692, 34680948, 15576456, 22218435, 15769976, 34440832, 36546343)
Labcorp Genetics (formerly Invitae), Labcorp RCV002264908 SCV003440998 uncertain significance not provided 2022-10-07 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 92 of the IGF1 protein (p.Val92Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with insulin-like growth factor I (IGF1) deficiency (PMID: 15769976). ClinVar contains an entry for this variant (Variation ID: 14789). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). Experimental studies have shown that this missense change affects IGF1 function (PMID: 15769976). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000015912 SCV000036179 pathogenic Growth delay due to insulin-like growth factor type 1 deficiency 2005-05-01 no assertion criteria provided literature only

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