ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.1244A>G (p.Tyr415Cys)

dbSNP: rs371321580
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498917 SCV000590052 uncertain significance not provided 2018-01-03 criteria provided, single submitter clinical testing The Y455C variant in the NRXN1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y455C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y455C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret Y455C as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001302540 SCV001491753 uncertain significance Pitt-Hopkins-like syndrome 2 2023-09-08 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 432336). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 455 of the NRXN1 protein (p.Tyr455Cys).
GenomeConnect, ClinGen RCV000509452 SCV000607249 not provided NRXN-related disorder no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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