Submissions for variant NM_170784.3(MKKS):c.1239_1242dup (p.Thr415Ter)

gnomAD frequency: 0.00001  dbSNP: rs1306231185

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003768093	SCV004574465	pathogenic	Bardet-Biedl syndrome; McKusick-Kaufman syndrome	2023-12-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr415*) in the MKKS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 156 amino acid(s) of the MKKS protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of Bardet-Biedl syndrome and/or cone rod dystrophy (PMID: 30614526, 30718709). ClinVar contains an entry for this variant (Variation ID: 585164). This variant disrupts a region of the MKKS protein in which other variant(s) (p.Ser479*) have been determined to be pathogenic (PMID: 15770229, 33138063). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University	RCV000735910	SCV000839541	pathogenic	Bardet-Biedl syndrome	2018-09-15	no assertion criteria provided	provider interpretation
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787851	SCV000926865	likely pathogenic	Progressive cone dystrophy (without rod involvement)	2018-04-01	no assertion criteria provided	research