TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15529	46810;46811;46812	chr2:178619732;178619731;178619730	chr2:179484459;179484458;179484457
N2AB	13888	41887;41888;41889	chr2:178619732;178619731;178619730	chr2:179484459;179484458;179484457
N2A	12961	39106;39107;39108	chr2:178619732;178619731;178619730	chr2:179484459;179484458;179484457
N2B	6464	19615;19616;19617	chr2:178619732;178619731;178619730	chr2:179484459;179484458;179484457
Novex-1	6589	19990;19991;19992	chr2:178619732;178619731;178619730	chr2:179484459;179484458;179484457
Novex-2	6656	20191;20192;20193	chr2:178619732;178619731;178619730	chr2:179484459;179484458;179484457
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-107
• Domain position: 50
• Structural Position: 127
• Q(SASA): 0.3361
• 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
S/N	None	None	0.999	D	0.713	0.26	0.326881540566	gnomAD-4.0.0	6.84693E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00033E-07	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
S/A	0.1375	likely_benign	0.1792	benign	-0.381	Destabilizing	0.998	D	0.582	neutral	None	None	None	None	N
S/C	0.2666	likely_benign	0.3595	ambiguous	-0.232	Destabilizing	1.0	D	0.757	deleterious	N	0.510955798	None	None	N
S/D	0.6163	likely_pathogenic	0.7218	pathogenic	-0.111	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
S/E	0.716	likely_pathogenic	0.8115	pathogenic	-0.179	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
S/F	0.6211	likely_pathogenic	0.6864	pathogenic	-0.777	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
S/G	0.2059	likely_benign	0.2864	benign	-0.553	Destabilizing	0.999	D	0.647	neutral	D	0.54055012	None	None	N
S/H	0.633	likely_pathogenic	0.6895	pathogenic	-1.066	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
S/I	0.4499	ambiguous	0.5203	ambiguous	-0.052	Destabilizing	1.0	D	0.802	deleterious	N	0.502100758	None	None	N
S/K	0.8676	likely_pathogenic	0.912	pathogenic	-0.678	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
S/L	0.3	likely_benign	0.3395	benign	-0.052	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
S/M	0.3906	ambiguous	0.4533	ambiguous	0.191	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
S/N	0.2541	likely_benign	0.34	ambiguous	-0.385	Destabilizing	0.999	D	0.713	prob.delet.	D	0.536114762	None	None	N
S/P	0.7782	likely_pathogenic	0.845	pathogenic	-0.13	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
S/Q	0.6827	likely_pathogenic	0.752	pathogenic	-0.606	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
S/R	0.8257	likely_pathogenic	0.8725	pathogenic	-0.459	Destabilizing	1.0	D	0.781	deleterious	N	0.494406951	None	None	N
S/T	0.118	likely_benign	0.1423	benign	-0.433	Destabilizing	0.999	D	0.662	neutral	N	0.503917449	None	None	N
S/V	0.3673	ambiguous	0.4288	ambiguous	-0.13	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
S/W	0.7068	likely_pathogenic	0.7302	pathogenic	-0.801	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
S/Y	0.5234	ambiguous	0.5683	pathogenic	-0.54	Destabilizing	1.0	D	0.818	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.