Submissions for variant NM_016247.4(IMPG2):c.1223C>T (p.Thr408Met)

gnomAD frequency: 0.00032  dbSNP: rs148056371

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000375226	SCV000439570	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000949263	SCV001095513	likely benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001000670	SCV001157700	uncertain significance	not specified	2019-05-05	criteria provided, single submitter	clinical testing	The IMPG2 c.1223C>T; p.Thr408Met variant (rs148056371), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is reported in the ClinVar database (Variation ID: 342352) and in the Latino population with an allele frequency of 0.4% (130/35022 alleles) in the Genome Aggregation Database. The amino acid at this position is moderately conserved and computational analyses (SIFT: Tolerated, PolyPhen-2: Possibly Damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the variant is uncertain at this time.
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000949263	SCV001448866	benign	not provided	2019-03-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000949263	SCV005093408	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	IMPG2: BP4
PreventionGenetics, part of Exact Sciences	RCV004757214	SCV005350505	likely benign	IMPG2-related disorder	2024-09-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).