TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14703	44332;44333;44334	chr2:178630851;178630850;178630849	chr2:179495578;179495577;179495576
N2AB	13062	39409;39410;39411	chr2:178630851;178630850;178630849	chr2:179495578;179495577;179495576
N2A	12135	36628;36629;36630	chr2:178630851;178630850;178630849	chr2:179495578;179495577;179495576
N2B	5638	17137;17138;17139	chr2:178630851;178630850;178630849	chr2:179495578;179495577;179495576
Novex-1	5763	17512;17513;17514	chr2:178630851;178630850;178630849	chr2:179495578;179495577;179495576
Novex-2	5830	17713;17714;17715	chr2:178630851;178630850;178630849	chr2:179495578;179495577;179495576
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-98
• Domain position: 29
• Structural Position: 44
• Q(SASA): 0.2012
• 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
I/S	rs2059714410	None	0.664	N	0.445	0.325	0.490701487448	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/S	rs2059714410	None	0.664	N	0.445	0.325	0.490701487448	gnomAD-4.0.0	6.57575E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47024E-05	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
I/A	0.631	likely_pathogenic	0.7378	pathogenic	-1.426	Destabilizing	0.134	N	0.393	neutral	None	None	None	None	N
I/C	0.7752	likely_pathogenic	0.8631	pathogenic	-0.503	Destabilizing	0.984	D	0.397	neutral	None	None	None	None	N
I/D	0.8795	likely_pathogenic	0.9466	pathogenic	-1.243	Destabilizing	0.942	D	0.601	neutral	None	None	None	None	N
I/E	0.8305	likely_pathogenic	0.8982	pathogenic	-1.267	Destabilizing	0.842	D	0.527	neutral	None	None	None	None	N
I/F	0.2789	likely_benign	0.3309	benign	-1.174	Destabilizing	0.664	D	0.407	neutral	N	0.423861063	None	None	N
I/G	0.8547	likely_pathogenic	0.9269	pathogenic	-1.701	Destabilizing	0.842	D	0.5	neutral	None	None	None	None	N
I/H	0.7628	likely_pathogenic	0.8553	pathogenic	-1.11	Destabilizing	0.984	D	0.571	neutral	None	None	None	None	N
I/K	0.644	likely_pathogenic	0.7835	pathogenic	-0.935	Destabilizing	0.842	D	0.511	neutral	None	None	None	None	N
I/L	0.1603	likely_benign	0.1949	benign	-0.746	Destabilizing	0.001	N	0.104	neutral	N	0.4318099	None	None	N
I/M	0.2012	likely_benign	0.2407	benign	-0.488	Destabilizing	0.664	D	0.48	neutral	N	0.438126183	None	None	N
I/N	0.5046	ambiguous	0.6948	pathogenic	-0.561	Destabilizing	0.924	D	0.581	neutral	N	0.424921435	None	None	N
I/P	0.8961	likely_pathogenic	0.9555	pathogenic	-0.944	Destabilizing	0.942	D	0.605	neutral	None	None	None	None	N
I/Q	0.7366	likely_pathogenic	0.844	pathogenic	-0.764	Destabilizing	0.942	D	0.571	neutral	None	None	None	None	N
I/R	0.567	likely_pathogenic	0.7053	pathogenic	-0.389	Destabilizing	0.842	D	0.585	neutral	None	None	None	None	N
I/S	0.5321	ambiguous	0.6909	pathogenic	-0.984	Destabilizing	0.664	D	0.445	neutral	N	0.43479856	None	None	N
I/T	0.4055	ambiguous	0.5188	ambiguous	-0.901	Destabilizing	0.361	N	0.445	neutral	N	0.436425782	None	None	N
I/V	0.0894	likely_benign	0.0959	benign	-0.944	Destabilizing	None	N	0.105	neutral	N	0.330138194	None	None	N
I/W	0.9075	likely_pathogenic	0.9436	pathogenic	-1.267	Destabilizing	0.984	D	0.651	prob.neutral	None	None	None	None	N
I/Y	0.6912	likely_pathogenic	0.8145	pathogenic	-1.047	Destabilizing	0.842	D	0.425	neutral	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.