ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.6026G>A (p.Gly2009Asp)

dbSNP: rs1842960290
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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 RCV003587145 SCV004281583 uncertain significance Adams-Oliver syndrome 5 2023-06-09 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NOTCH1 protein function. 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. This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2009 of the NOTCH1 protein (p.Gly2009Asp).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004801362 SCV005422761 uncertain significance not specified 2024-10-30 criteria provided, single submitter clinical testing Variant summary: NOTCH1 c.6026G>A (p.Gly2009Asp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.6026G>A in individuals affected with Adams-Oliver Syndrome 5 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2724797). Based on the evidence outlined above, the variant was classified as uncertain significance.

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