ClinVar Miner

Submissions for variant NM_022455.4(NSD1):c.6605G>A (p.Cys2202Tyr) (rs121908071)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001043020 SCV001206731 pathogenic Beckwith-Wiedemann syndrome 2019-12-06 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 2202 of the NSD1 protein (p.Cys2202Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Sotos syndrome (PMID: 16222665, 25533962, 29276005). It has also been observed to segregate with an overgrowth phenotype in related individuals. ClinVar contains an entry for this variant (Variation ID: 4146). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Cys2202 amino acid residue in NSD1. Other variant(s) that disrupt this residue have been observed in individuals with NSD1-related conditions (PMID: 29264563, 15452385), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004362 SCV000024533 pathogenic Sotos syndrome 1 2017-09-25 no assertion criteria provided literature only

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