TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23108	69547;69548;69549	chr2:178577013;178577012;178577011	chr2:179441740;179441739;179441738
N2AB	21467	64624;64625;64626	chr2:178577013;178577012;178577011	chr2:179441740;179441739;179441738
N2A	20540	61843;61844;61845	chr2:178577013;178577012;178577011	chr2:179441740;179441739;179441738
N2B	14043	42352;42353;42354	chr2:178577013;178577012;178577011	chr2:179441740;179441739;179441738
Novex-1	14168	42727;42728;42729	chr2:178577013;178577012;178577011	chr2:179441740;179441739;179441738
Novex-2	14235	42928;42929;42930	chr2:178577013;178577012;178577011	chr2:179441740;179441739;179441738
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-55
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.3436
• 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
N/K	rs147525123	-0.345	0.067	N	0.319	0.077	0.112648838833	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
N/K	rs147525123	-0.345	0.067	N	0.319	0.077	0.112648838833	gnomAD-4.0.0	6.84321E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99607E-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
N/A	0.8928	likely_pathogenic	0.8754	pathogenic	-0.947	Destabilizing	0.938	D	0.581	neutral	None	None	None	None	N
N/C	0.7081	likely_pathogenic	0.6831	pathogenic	-0.083	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
N/D	0.8647	likely_pathogenic	0.8745	pathogenic	-0.713	Destabilizing	0.958	D	0.499	neutral	N	0.486826467	None	None	N
N/E	0.9623	likely_pathogenic	0.9639	pathogenic	-0.592	Destabilizing	0.938	D	0.509	neutral	None	None	None	None	N
N/F	0.9755	likely_pathogenic	0.9654	pathogenic	-0.546	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
N/G	0.8429	likely_pathogenic	0.8272	pathogenic	-1.312	Destabilizing	0.968	D	0.425	neutral	None	None	None	None	N
N/H	0.4765	ambiguous	0.4485	ambiguous	-0.964	Destabilizing	0.994	D	0.667	neutral	N	0.494911296	None	None	N
N/I	0.921	likely_pathogenic	0.9176	pathogenic	-0.003	Destabilizing	0.994	D	0.735	prob.delet.	N	0.477609755	None	None	N
N/K	0.952	likely_pathogenic	0.9455	pathogenic	-0.444	Destabilizing	0.067	N	0.319	neutral	N	0.487771893	None	None	N
N/L	0.9001	likely_pathogenic	0.8641	pathogenic	-0.003	Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	N
N/M	0.919	likely_pathogenic	0.8914	pathogenic	0.387	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
N/P	0.9873	likely_pathogenic	0.9875	pathogenic	-0.288	Destabilizing	0.995	D	0.666	neutral	None	None	None	None	N
N/Q	0.9075	likely_pathogenic	0.8958	pathogenic	-0.965	Destabilizing	0.991	D	0.667	neutral	None	None	None	None	N
N/R	0.9255	likely_pathogenic	0.9164	pathogenic	-0.493	Destabilizing	0.982	D	0.577	neutral	None	None	None	None	N
N/S	0.3279	likely_benign	0.3252	benign	-1.083	Destabilizing	0.958	D	0.411	neutral	N	0.485192947	None	None	N
N/T	0.8092	likely_pathogenic	0.8018	pathogenic	-0.77	Destabilizing	0.958	D	0.558	neutral	N	0.431526247	None	None	N
N/V	0.903	likely_pathogenic	0.8917	pathogenic	-0.288	Destabilizing	0.991	D	0.715	prob.delet.	None	None	None	None	N
N/W	0.9858	likely_pathogenic	0.9815	pathogenic	-0.314	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
N/Y	0.7754	likely_pathogenic	0.744	pathogenic	-0.119	Destabilizing	0.998	D	0.712	prob.delet.	N	0.510210641	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.