Submissions for variant NM_022455.5(NSD1):c.3556_3557delinsAT (p.Ala1186Ile)

dbSNP: rs797044760

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000178992	SCV000231178	uncertain significance	not provided	2015-01-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000690126	SCV000817804	uncertain significance	Beckwith-Wiedemann syndrome	2018-09-04	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with isoleucine at codon 1186 of the NSD1 protein (p.Ala1186Ile). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NSD1-related disease. ClinVar contains an entry for this variant (Variation ID: 197855). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003231362	SCV001517078	uncertain significance	Sotos syndrome	2021-08-31	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003231362	SCV002054901	uncertain significance	Sotos syndrome	2021-07-15	criteria provided, single submitter	clinical testing