TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26335	79228;79229;79230	chr2:178567129;178567128;178567127	chr2:179431856;179431855;179431854
N2AB	24694	74305;74306;74307	chr2:178567129;178567128;178567127	chr2:179431856;179431855;179431854
N2A	23767	71524;71525;71526	chr2:178567129;178567128;178567127	chr2:179431856;179431855;179431854
N2B	17270	52033;52034;52035	chr2:178567129;178567128;178567127	chr2:179431856;179431855;179431854
Novex-1	17395	52408;52409;52410	chr2:178567129;178567128;178567127	chr2:179431856;179431855;179431854
Novex-2	17462	52609;52610;52611	chr2:178567129;178567128;178567127	chr2:179431856;179431855;179431854
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-79
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.363
• Predicted PPI site: I

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
T/I	None	None	0.994	N	0.741	0.493	0.56369308836	gnomAD-4.0.0	1.59182E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02554E-05
T/S	None	None	0.234	N	0.325	0.251	0.232513804876	gnomAD-4.0.0	3.18364E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.8659E-05	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
T/A	0.3363	likely_benign	0.4423	ambiguous	-0.511	Destabilizing	0.825	D	0.555	neutral	N	0.497084809	None	None	I
T/C	0.8473	likely_pathogenic	0.9041	pathogenic	-0.436	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
T/D	0.9561	likely_pathogenic	0.9785	pathogenic	0.253	Stabilizing	0.991	D	0.689	prob.neutral	None	None	None	None	I
T/E	0.9328	likely_pathogenic	0.9658	pathogenic	0.236	Stabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	I
T/F	0.856	likely_pathogenic	0.9138	pathogenic	-0.701	Destabilizing	0.995	D	0.747	deleterious	None	None	None	None	I
T/G	0.7139	likely_pathogenic	0.793	pathogenic	-0.727	Destabilizing	0.938	D	0.603	neutral	None	None	None	None	I
T/H	0.8324	likely_pathogenic	0.8944	pathogenic	-0.896	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
T/I	0.7025	likely_pathogenic	0.7861	pathogenic	-0.044	Destabilizing	0.994	D	0.741	deleterious	N	0.492217707	None	None	I
T/K	0.8967	likely_pathogenic	0.9342	pathogenic	-0.487	Destabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	I
T/L	0.4433	ambiguous	0.5859	pathogenic	-0.044	Destabilizing	0.968	D	0.611	neutral	None	None	None	None	I
T/M	0.2111	likely_benign	0.3047	benign	-0.072	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
T/N	0.5007	ambiguous	0.6348	pathogenic	-0.421	Destabilizing	0.988	D	0.684	prob.neutral	N	0.472214477	None	None	I
T/P	0.9201	likely_pathogenic	0.9107	pathogenic	-0.167	Destabilizing	0.994	D	0.737	prob.delet.	N	0.510223867	None	None	I
T/Q	0.7932	likely_pathogenic	0.8662	pathogenic	-0.534	Destabilizing	0.991	D	0.73	prob.delet.	None	None	None	None	I
T/R	0.8629	likely_pathogenic	0.9019	pathogenic	-0.253	Destabilizing	0.991	D	0.727	prob.delet.	None	None	None	None	I
T/S	0.4177	ambiguous	0.5229	ambiguous	-0.687	Destabilizing	0.234	N	0.325	neutral	N	0.516460004	None	None	I
T/V	0.4726	ambiguous	0.5514	ambiguous	-0.167	Destabilizing	0.968	D	0.597	neutral	None	None	None	None	I
T/W	0.9646	likely_pathogenic	0.9754	pathogenic	-0.698	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
T/Y	0.886	likely_pathogenic	0.9322	pathogenic	-0.43	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	I

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.