ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.270G>T (p.Gln90His) (rs199960045)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000656993 SCV000227213 uncertain significance not provided 2015-05-14 criteria provided, single submitter clinical testing
GeneDx RCV000656993 SCV000565686 uncertain significance not provided 2017-12-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NRXN1 gene. The Q90H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q90H variant is observed in 4/34094 (0.01%) alleles from individuals of Latino background (Lek et al., 2016). The Q90H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Fulgent Genetics,Fulgent Genetics RCV000765689 SCV000897031 uncertain significance Pitt-Hopkins-like syndrome 2; Schizophrenia 17 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001035816 SCV001199154 uncertain significance Pitt-Hopkins-like syndrome 2 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 90 of the NRXN1 protein (p.Gln90His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs199960045, ExAC 0.01%). This variant has not been reported in the literature in individuals with NRXN1-related disease. ClinVar contains an entry for this variant (Variation ID: 195130). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

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