TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23241	69946;69947;69948	chr2:178576411;178576410;178576409	chr2:179441138;179441137;179441136
N2AB	21600	65023;65024;65025	chr2:178576411;178576410;178576409	chr2:179441138;179441137;179441136
N2A	20673	62242;62243;62244	chr2:178576411;178576410;178576409	chr2:179441138;179441137;179441136
N2B	14176	42751;42752;42753	chr2:178576411;178576410;178576409	chr2:179441138;179441137;179441136
Novex-1	14301	43126;43127;43128	chr2:178576411;178576410;178576409	chr2:179441138;179441137;179441136
Novex-2	14368	43327;43328;43329	chr2:178576411;178576410;178576409	chr2:179441138;179441137;179441136
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: Fn3-57
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.133
• 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/S	None	None	1.0	N	0.772	0.533	0.484256599201	gnomAD-4.0.0	1.69731E-06	None	None	None	None	N	None	6.58155E-05	0	None	0	0	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	0.6998	likely_pathogenic	0.6643	pathogenic	-1.936	Destabilizing	0.999	D	0.807	deleterious	D	0.526311249	None	None	N
P/C	0.979	likely_pathogenic	0.9761	pathogenic	-1.973	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.999	pathogenic	-3.188	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/E	0.9974	likely_pathogenic	0.9969	pathogenic	-3.081	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/F	0.9994	likely_pathogenic	0.9993	pathogenic	-1.181	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/G	0.989	likely_pathogenic	0.9862	pathogenic	-2.319	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/H	0.9967	likely_pathogenic	0.9959	pathogenic	-1.781	Destabilizing	1.0	D	0.739	deleterious	None	None	None	None	N
P/I	0.9915	likely_pathogenic	0.9909	pathogenic	-0.908	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
P/K	0.998	likely_pathogenic	0.9974	pathogenic	-1.653	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
P/L	0.9631	likely_pathogenic	0.9585	pathogenic	-0.908	Destabilizing	1.0	D	0.819	deleterious	D	0.52580427	None	None	N
P/M	0.9954	likely_pathogenic	0.995	pathogenic	-1.122	Destabilizing	1.0	D	0.737	deleterious	None	None	None	None	N
P/N	0.9992	likely_pathogenic	0.9989	pathogenic	-1.912	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/Q	0.9943	likely_pathogenic	0.9932	pathogenic	-1.972	Destabilizing	1.0	D	0.825	deleterious	D	0.538681513	None	None	N
P/R	0.9909	likely_pathogenic	0.9879	pathogenic	-1.259	Destabilizing	1.0	D	0.797	deleterious	D	0.538174534	None	None	N
P/S	0.9628	likely_pathogenic	0.9568	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.772	deleterious	N	0.510916019	None	None	N
P/T	0.9691	likely_pathogenic	0.9661	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.779	deleterious	N	0.520070279	None	None	N
P/V	0.9654	likely_pathogenic	0.9633	pathogenic	-1.225	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.56	Destabilizing	1.0	D	0.725	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9992	pathogenic	-1.282	Destabilizing	1.0	D	0.803	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.