TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20435	61528;61529;61530	chr2:178590422;178590421;178590420	chr2:179455149;179455148;179455147
N2AB	18794	56605;56606;56607	chr2:178590422;178590421;178590420	chr2:179455149;179455148;179455147
N2A	17867	53824;53825;53826	chr2:178590422;178590421;178590420	chr2:179455149;179455148;179455147
N2B	11370	34333;34334;34335	chr2:178590422;178590421;178590420	chr2:179455149;179455148;179455147
Novex-1	11495	34708;34709;34710	chr2:178590422;178590421;178590420	chr2:179455149;179455148;179455147
Novex-2	11562	34909;34910;34911	chr2:178590422;178590421;178590420	chr2:179455149;179455148;179455147
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-36
• Domain position: 65
• Structural Position: 94
• Q(SASA): 0.4455
• 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	0.978	N	0.599	0.327	0.327952845175	gnomAD-4.0.0	1.5969E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86507E-06	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	0.1143	likely_benign	0.1125	benign	-0.94	Destabilizing	0.978	D	0.513	neutral	N	0.508648597	None	None	N
P/C	0.6183	likely_pathogenic	0.6274	pathogenic	-0.877	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
P/D	0.5301	ambiguous	0.5171	ambiguous	-0.429	Destabilizing	0.998	D	0.65	neutral	None	None	None	None	N
P/E	0.3489	ambiguous	0.3394	benign	-0.435	Destabilizing	0.983	D	0.551	neutral	None	None	None	None	N
P/F	0.6881	likely_pathogenic	0.6735	pathogenic	-0.689	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
P/G	0.3629	ambiguous	0.3612	ambiguous	-1.201	Destabilizing	0.992	D	0.623	neutral	None	None	None	None	N
P/H	0.2768	likely_benign	0.2764	benign	-0.501	Destabilizing	1.0	D	0.737	prob.delet.	N	0.501722625	None	None	N
P/I	0.4787	ambiguous	0.4454	ambiguous	-0.343	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
P/K	0.3468	ambiguous	0.3307	benign	-0.753	Destabilizing	0.246	N	0.314	neutral	None	None	None	None	N
P/L	0.1981	likely_benign	0.1909	benign	-0.343	Destabilizing	0.997	D	0.679	prob.neutral	N	0.502069341	None	None	N
P/M	0.4353	ambiguous	0.4231	ambiguous	-0.541	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
P/N	0.3932	ambiguous	0.3948	ambiguous	-0.665	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
P/Q	0.2219	likely_benign	0.2213	benign	-0.761	Destabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	N
P/R	0.2656	likely_benign	0.2551	benign	-0.304	Destabilizing	0.987	D	0.653	neutral	N	0.484251585	None	None	N
P/S	0.1583	likely_benign	0.1563	benign	-1.175	Destabilizing	0.978	D	0.599	neutral	N	0.450984373	None	None	N
P/T	0.1208	likely_benign	0.1127	benign	-1.055	Destabilizing	0.989	D	0.631	neutral	N	0.419506673	None	None	N
P/V	0.3243	likely_benign	0.2984	benign	-0.507	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
P/W	0.768	likely_pathogenic	0.7543	pathogenic	-0.809	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
P/Y	0.6328	likely_pathogenic	0.6094	pathogenic	-0.516	Destabilizing	0.999	D	0.763	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.