Submissions for variant NM_022455.5(NSD1):c.8071G>A (p.Ala2691Thr)

gnomAD frequency: 0.00018  dbSNP: rs201823140

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153613	SCV000203159	uncertain significance	not provided	2014-04-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003231346	SCV000829764	uncertain significance	Sotos syndrome	2021-08-30	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with threonine at codon 2691 of the NSD1 protein (p.Ala2691Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs201823140, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with NSD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 167395). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.
Genome-Nilou Lab	RCV003231346	SCV002054911	uncertain significance	Sotos syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV003231346	SCV002792373	uncertain significance	Sotos syndrome	2022-02-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000153613	SCV004702658	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	NSD1: BS2