TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24932	75019;75020;75021	chr2:178571338;178571337;178571336	chr2:179436065;179436064;179436063
N2AB	23291	70096;70097;70098	chr2:178571338;178571337;178571336	chr2:179436065;179436064;179436063
N2A	22364	67315;67316;67317	chr2:178571338;178571337;178571336	chr2:179436065;179436064;179436063
N2B	15867	47824;47825;47826	chr2:178571338;178571337;178571336	chr2:179436065;179436064;179436063
Novex-1	15992	48199;48200;48201	chr2:178571338;178571337;178571336	chr2:179436065;179436064;179436063
Novex-2	16059	48400;48401;48402	chr2:178571338;178571337;178571336	chr2:179436065;179436064;179436063
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-69
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1542
• 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
P/A	rs878982463	None	1.0	D	0.833	0.752	0.582924345863	gnomAD-4.0.0	1.77929E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.33898E-05	0	0
P/S	rs878982463	None	1.0	D	0.858	0.688	0.561065777782	gnomAD-4.0.0	6.84341E-07	None	None	None	None	N	None	0	0	None	0	2.52143E-05	None	0	0	0	0	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
P/A	0.8812	likely_pathogenic	0.8754	pathogenic	-1.818	Destabilizing	1.0	D	0.833	deleterious	D	0.590419284	None	None	N
P/C	0.9817	likely_pathogenic	0.9817	pathogenic	-1.181	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/D	0.9977	likely_pathogenic	0.9969	pathogenic	-1.947	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/E	0.9964	likely_pathogenic	0.9955	pathogenic	-1.91	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/F	0.9992	likely_pathogenic	0.9991	pathogenic	-1.382	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/G	0.9828	likely_pathogenic	0.9803	pathogenic	-2.192	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/H	0.9953	likely_pathogenic	0.9941	pathogenic	-1.855	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/I	0.9911	likely_pathogenic	0.9905	pathogenic	-0.857	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/K	0.9979	likely_pathogenic	0.9973	pathogenic	-1.586	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/L	0.9671	likely_pathogenic	0.964	pathogenic	-0.857	Destabilizing	1.0	D	0.899	deleterious	D	0.64968199	None	None	N
P/M	0.9939	likely_pathogenic	0.9926	pathogenic	-0.595	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/N	0.9952	likely_pathogenic	0.9937	pathogenic	-1.397	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/Q	0.9947	likely_pathogenic	0.9938	pathogenic	-1.525	Destabilizing	1.0	D	0.84	deleterious	D	0.650691012	None	None	N
P/R	0.9936	likely_pathogenic	0.9928	pathogenic	-1.093	Destabilizing	1.0	D	0.894	deleterious	D	0.634237682	None	None	N
P/S	0.9748	likely_pathogenic	0.9684	pathogenic	-1.909	Destabilizing	1.0	D	0.858	deleterious	D	0.575853631	None	None	N
P/T	0.9679	likely_pathogenic	0.963	pathogenic	-1.758	Destabilizing	1.0	D	0.855	deleterious	D	0.618016517	None	None	N
P/V	0.9709	likely_pathogenic	0.9706	pathogenic	-1.144	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9996	pathogenic	-1.663	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/Y	0.9989	likely_pathogenic	0.9987	pathogenic	-1.375	Destabilizing	1.0	D	0.897	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.