TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26272	79039;79040;79041	chr2:178567318;178567317;178567316	chr2:179432045;179432044;179432043
N2AB	24631	74116;74117;74118	chr2:178567318;178567317;178567316	chr2:179432045;179432044;179432043
N2A	23704	71335;71336;71337	chr2:178567318;178567317;178567316	chr2:179432045;179432044;179432043
N2B	17207	51844;51845;51846	chr2:178567318;178567317;178567316	chr2:179432045;179432044;179432043
Novex-1	17332	52219;52220;52221	chr2:178567318;178567317;178567316	chr2:179432045;179432044;179432043
Novex-2	17399	52420;52421;52422	chr2:178567318;178567317;178567316	chr2:179432045;179432044;179432043
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-137
• Domain position: 80
• Structural Position: 163
• Q(SASA): 0.2606
• 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
A/V	None	None	0.994	D	0.651	0.365	0.44750879378	gnomAD-4.0.0	2.06366E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.70483E-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
A/C	0.7024	likely_pathogenic	0.6759	pathogenic	-0.948	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
A/D	0.9541	likely_pathogenic	0.9501	pathogenic	-0.471	Destabilizing	0.991	D	0.69	prob.neutral	None	None	None	None	I
A/E	0.9331	likely_pathogenic	0.9277	pathogenic	-0.608	Destabilizing	0.994	D	0.673	neutral	N	0.505384108	None	None	I
A/F	0.698	likely_pathogenic	0.6739	pathogenic	-0.957	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
A/G	0.1849	likely_benign	0.1556	benign	-0.321	Destabilizing	0.029	N	0.344	neutral	N	0.521015754	None	None	I
A/H	0.9099	likely_pathogenic	0.913	pathogenic	-0.271	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
A/I	0.8126	likely_pathogenic	0.7983	pathogenic	-0.5	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	I
A/K	0.9704	likely_pathogenic	0.9695	pathogenic	-0.571	Destabilizing	0.991	D	0.672	neutral	None	None	None	None	I
A/L	0.616	likely_pathogenic	0.6098	pathogenic	-0.5	Destabilizing	0.995	D	0.605	neutral	None	None	None	None	I
A/M	0.6928	likely_pathogenic	0.67	pathogenic	-0.666	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
A/N	0.857	likely_pathogenic	0.8519	pathogenic	-0.329	Destabilizing	0.991	D	0.689	prob.neutral	None	None	None	None	I
A/P	0.9646	likely_pathogenic	0.9643	pathogenic	-0.418	Destabilizing	0.998	D	0.684	prob.neutral	N	0.51980506	None	None	I
A/Q	0.8906	likely_pathogenic	0.8903	pathogenic	-0.553	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	I
A/R	0.9306	likely_pathogenic	0.9291	pathogenic	-0.177	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	I
A/S	0.1915	likely_benign	0.1866	benign	-0.541	Destabilizing	0.958	D	0.547	neutral	N	0.493240881	None	None	I
A/T	0.4534	ambiguous	0.4381	ambiguous	-0.603	Destabilizing	0.994	D	0.653	neutral	N	0.518978459	None	None	I
A/V	0.5238	ambiguous	0.4909	ambiguous	-0.418	Destabilizing	0.994	D	0.651	neutral	D	0.523322553	None	None	I
A/W	0.9667	likely_pathogenic	0.9614	pathogenic	-1.038	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
A/Y	0.8721	likely_pathogenic	0.8631	pathogenic	-0.749	Destabilizing	1.0	D	0.721	prob.delet.	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.