ClinVar Miner

Submissions for variant NM_022455.5(NSD1):c.5127G>A (p.Trp1709Ter)

dbSNP: rs2149918110
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003232470 SCV002207041 pathogenic Sotos syndrome 2022-10-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1709*) in the NSD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NSD1 are known to be pathogenic (PMID: 12464997, 14571271, 15942875, 16247291). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Sotos syndrome (PMID: 15720303). ClinVar contains an entry for this variant (Variation ID: 1425282). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002344062 SCV002645598 pathogenic Inborn genetic diseases 2016-03-23 criteria provided, single submitter clinical testing The p.W1709* pathogenic mutation (also known as c.5127G>A), located in coding exon 13 of the NSD1 gene, results from a G to A substitution at nucleotide position 5127. This changes the amino acid from a tryptophan to a stop codon within coding exon 13. This pathogenic mutation was detected in an individual with Sotos syndrome (Melchior L et al. Ann. Hum. Genet. 2005 Mar; 69 (Pt 2):222-6). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

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