Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003058357 | SCV003440958 | likely pathogenic | not provided | 2022-09-19 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the NECTIN1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NECTIN1 are known to be pathogenic (PMID: 10932188, 25913853). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is also known as IVS4+1G>A in PVRL1. Disruption of this splice site has been observed in individual(s) with nonsyndromic cleft lip with or without cleft palate (PMID: 19715471). This variant is present in population databases (no rsID available, gnomAD 0.009%). |
| Gene |
RCV003058357 | SCV005325060 | uncertain significance | not provided | 2024-02-07 | criteria provided, single submitter | clinical testing | Identified in the heterozygous state in a patient with nonsyndromic cleft lip/palate in published literature, but it is unknown whether this individual was screened for variants in other genes associated with cleft lip/palate (PMID: 19715471); Canonical splice site variant in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 22978696, 19715471) |