Submissions for variant NM_001128178.3(NPHP1):c.1936C>T (p.Leu646Phe)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002800944	SCV003034953	uncertain significance	Nephronophthisis	2022-10-04	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 702 of the NPHP1 protein (p.Leu702Phe). This variant is present in population databases (rs748152745, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NPHP1-related conditions. 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 NPHP1 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.
Fulgent Genetics, Fulgent Genetics	RCV005019403	SCV005651110	uncertain significance	Joubert syndrome with renal defect; Nephronophthisis 1; Senior-Loken syndrome 1	2024-06-15	criteria provided, single submitter	clinical testing