ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.570C>A (p.Asn190Lys) (rs564945882)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188274 SCV000241884 uncertain significance not provided 2012-09-26 criteria provided, single submitter clinical testing The Asn190Lys missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Asn190Lys in approximately 6,200 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as an uncharged Asparagine residue is replaced by a positively charged Lysine residue. Asn190Lys alters a position that is not conserved in the neurexin1 protein but is highly conserved in related proteins, and several in silico algorithms predict Asn190Lys may be damaging to protein structure/function. Therefore, based on the currently available information, it is unclear whether Asn190Lys is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000818582 SCV000959202 uncertain significance Pitt-Hopkins-like syndrome 2 2018-08-22 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 190 of the NRXN1 protein (p.Asn190Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs564945882, ExAC 0.03%). This variant has not been reported in the literature in individuals with NRXN1-related disease. ClinVar contains an entry for this variant (Variation ID: 206244). 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: "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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