Submissions for variant NM_001354930.2(RIPK1):c.1122_1123delinsAA (p.Gln375Lys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003680307	SCV004408576	uncertain significance	not provided	2022-10-27	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 RIPK1-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 375 of the RIPK1 protein (p.Gln375Lys).
Neuberg Centre For Genomic Medicine, NCGM	RCV004546804	SCV005042893	uncertain significance	Immunodeficiency 57		criteria provided, single submitter	clinical testing	The missense c.1123C>Ap.Gln375Lys variant in RIPK1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency of 0.0004% in the gnomAD Exomes and novel in 1000 Genomes. The amino acid Gln at position 375 is changed to a Lys changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Gln375Lys in RIPK1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The variant is predicted as damaging by SIFT. For these reasons, this variant has been classified as Uncertain Significance.