Submissions for variant NM_000208.4(INSR):c.3809G>A (p.Arg1270His)

gnomAD frequency: 0.00005  dbSNP: rs746000108

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000996723	SCV001151603	uncertain significance	not provided	2019-02-01	criteria provided, single submitter	clinical testing
Invitae	RCV000996723	SCV004321913	uncertain significance	not provided	2023-02-24	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1270 of the INSR protein (p.Arg1270His). This variant is present in population databases (rs746000108, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with INSR-related conditions. ClinVar contains an entry for this variant (Variation ID: 808429). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt INSR protein function. 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.