Submissions for variant NM_032575.3(GLIS2):c.1393C>G (p.Leu465Val)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003747875	SCV004464165	uncertain significance	Nephronophthisis	2023-07-09	criteria provided, single submitter	clinical testing	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with GLIS2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 465 of the GLIS2 protein (p.Leu465Val).
Ambry Genetics	RCV004634325	SCV005123639	uncertain significance	not specified	2024-03-31	criteria provided, single submitter	clinical testing	The c.1393C>G (p.L465V) alteration is located in exon 6 (coding exon 6) of the GLIS2 gene. This alteration results from a C to G substitution at nucleotide position 1393, causing the leucine (L) at amino acid position 465 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV004780623	SCV005392156	uncertain significance	not provided	2024-04-19	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV005014874	SCV005646879	uncertain significance	Nephronophthisis 7	2024-03-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004756530	SCV005363116	uncertain significance	GLIS2-related disorder	2024-03-11	no assertion criteria provided	clinical testing	The GLIS2 c.1393C>G variant is predicted to result in the amino acid substitution p.Leu465Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.