Submissions for variant NM_170784.3(MKKS):c.295T>C (p.Cys99Arg)

dbSNP: rs1297985227

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002534487	SCV003300677	likely pathogenic	Bardet-Biedl syndrome; McKusick-Kaufman syndrome	2023-07-25	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 585166). 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. 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 expected to disrupt MKKS protein function. This missense change has been observed in individuals with clinical features of MKKS-related conditions (PMID: 20472660, 26355662, 30614526). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 99 of the MKKS protein (p.Cys99Arg).
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV003987677	SCV004805108	likely pathogenic	McKusick-Kaufman syndrome	2024-03-17	criteria provided, single submitter	research
Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University	RCV000735912	SCV000839543	pathogenic	Bardet-Biedl syndrome	2018-09-15	no assertion criteria provided	provider interpretation