Submissions for variant NM_000883.4(IMPDH1):c.1714G>C (p.Glu572Gln)

gnomAD frequency: 0.00025  dbSNP: rs150628823

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000175021	SCV000226443	uncertain significance	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000284060	SCV000466733	uncertain significance	Retinitis pigmentosa	2018-01-13	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	RCV000339227	SCV000466734	uncertain significance	Leber congenital amaurosis 11	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000175021	SCV001372841	uncertain significance	not provided	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 572 of the IMPDH1 protein (p.Glu572Gln). This variant is present in population databases (rs150628823, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with IMPDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 194611). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Fulgent Genetics, Fulgent Genetics	RCV002492742	SCV002791772	uncertain significance	Retinitis pigmentosa 10; Leber congenital amaurosis 11	2022-05-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004020075	SCV004885615	uncertain significance	Inborn genetic diseases	2022-11-08	criteria provided, single submitter	clinical testing	The c.1714G>C (p.E572Q) alteration is located in exon 16 (coding exon 16) of the IMPDH1 gene. This alteration results from a G to C substitution at nucleotide position 1714, causing the glutamic acid (E) at amino acid position 572 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genetics, Academic Medical Center	RCV000175021	SCV001921730	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000175021	SCV001964508	likely benign	not provided		no assertion criteria provided	clinical testing