Submissions for variant NM_199242.3(UNC13D):c.71G>A (p.Arg24His)

gnomAD frequency: 0.00006  dbSNP: rs777619516

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000688781	SCV000816405	uncertain significance	Familial hemophagocytic lymphohistiocytosis 3	2025-01-31	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 24 of the UNC13D protein (p.Arg24His). This variant is present in population databases (rs777619516, gnomAD 0.03%). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 29665027). ClinVar contains an entry for this variant (Variation ID: 568424). 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 disruptive. 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.
GeneDx	RCV004777824	SCV005389739	uncertain significance	not provided	2024-04-30	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Identified as a single UNC13D variant in the heterozygous state in an individual with hemophagocytic lymphohistiocytosis (PMID: 29665027); This variant is associated with the following publications: (PMID: 29665027)
CeGaT Center for Human Genetics Tuebingen	RCV004777824	SCV005432419	uncertain significance	not provided	2024-09-01	criteria provided, single submitter	clinical testing	UNC13D: PM2, BP4