TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25288	76087;76088;76089	chr2:178570270;178570269;178570268	chr2:179434997;179434996;179434995
N2AB	23647	71164;71165;71166	chr2:178570270;178570269;178570268	chr2:179434997;179434996;179434995
N2A	22720	68383;68384;68385	chr2:178570270;178570269;178570268	chr2:179434997;179434996;179434995
N2B	16223	48892;48893;48894	chr2:178570270;178570269;178570268	chr2:179434997;179434996;179434995
Novex-1	16348	49267;49268;49269	chr2:178570270;178570269;178570268	chr2:179434997;179434996;179434995
Novex-2	16415	49468;49469;49470	chr2:178570270;178570269;178570268	chr2:179434997;179434996;179434995
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-71
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.12
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
G/D	None	None	1.0	D	0.899	0.712	0.537080035296	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
G/A	0.6902	likely_pathogenic	0.6969	pathogenic	-0.921	Destabilizing	1.0	D	0.707	prob.neutral	D	0.54896877	None	None	N
G/C	0.9165	likely_pathogenic	0.9324	pathogenic	-1.007	Destabilizing	1.0	D	0.89	deleterious	D	0.549982728	None	None	N
G/D	0.9896	likely_pathogenic	0.9902	pathogenic	-2.054	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.549475749	None	None	N
G/E	0.9924	likely_pathogenic	0.9936	pathogenic	-2.073	Highly Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
G/F	0.998	likely_pathogenic	0.9984	pathogenic	-1.067	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
G/H	0.9957	likely_pathogenic	0.9967	pathogenic	-1.619	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
G/I	0.9962	likely_pathogenic	0.9969	pathogenic	-0.432	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
G/K	0.9983	likely_pathogenic	0.9988	pathogenic	-1.525	Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
G/L	0.9936	likely_pathogenic	0.9948	pathogenic	-0.432	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
G/M	0.9945	likely_pathogenic	0.9954	pathogenic	-0.352	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
G/N	0.9872	likely_pathogenic	0.9894	pathogenic	-1.275	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
G/P	0.9991	likely_pathogenic	0.9993	pathogenic	-0.556	Destabilizing	1.0	D	0.932	deleterious	None	None	None	None	N
G/Q	0.9934	likely_pathogenic	0.9948	pathogenic	-1.445	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
G/R	0.994	likely_pathogenic	0.9953	pathogenic	-1.188	Destabilizing	1.0	D	0.939	deleterious	D	0.541713842	None	None	N
G/S	0.3203	likely_benign	0.3073	benign	-1.451	Destabilizing	1.0	D	0.833	deleterious	N	0.508387599	None	None	N
G/T	0.8973	likely_pathogenic	0.9136	pathogenic	-1.413	Destabilizing	1.0	D	0.932	deleterious	None	None	None	None	N
G/V	0.9878	likely_pathogenic	0.9903	pathogenic	-0.556	Destabilizing	1.0	D	0.935	deleterious	D	0.560832055	None	None	N
G/W	0.9932	likely_pathogenic	0.9944	pathogenic	-1.529	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
G/Y	0.9969	likely_pathogenic	0.9975	pathogenic	-1.131	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.