Submissions for variant NM_058246.4(DNAJB6):c.271T>G (p.Phe91Val)

dbSNP: rs869320701

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000591783	SCV000702873	likely pathogenic	not provided	2016-10-20	criteria provided, single submitter	clinical testing
Department of Medical Genetics, University of Pecs	RCV000845572	SCV000886727	likely pathogenic	Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	2018-12-05	criteria provided, single submitter	clinical testing	The patient's father is also affected with the same heterozygous mutation in the reported position, and they both have a milder phenotype of LGMD1D. LGMD1D cases were reported with different mutations in the same position resulting in more severe phenotype (Ruggieri et al. 2016, Palmio et al. 2015).
Invitae	RCV000845572	SCV002288744	likely pathogenic	Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	2022-08-04	criteria provided, single submitter	clinical testing	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. This variant disrupts the p.Phe91 amino acid residue in DNAJB6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26205529, 26338452, 26371419). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 DNAJB6 protein function. ClinVar contains an entry for this variant (Variation ID: 498056). This missense change has been observed in individual(s) with clinical features of DNAJB6-related conditions (PMID: 30564623, 31034989). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 91 of the DNAJB6 protein (p.Phe91Val).
CeGaT Center for Human Genetics Tuebingen	RCV000591783	SCV003917579	pathogenic	not provided	2023-01-01	criteria provided, single submitter	clinical testing	DNAJB6: PM1, PM2, PM5, PS4:Moderate, PP1, PP4
OMIM	RCV000845572	SCV002559812	pathogenic	Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	2022-08-09	no assertion criteria provided	literature only