TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14385	43378;43379;43380	chr2:178632978;178632977;178632976	chr2:179497705;179497704;179497703
N2AB	12744	38455;38456;38457	chr2:178632978;178632977;178632976	chr2:179497705;179497704;179497703
N2A	11817	35674;35675;35676	chr2:178632978;178632977;178632976	chr2:179497705;179497704;179497703
N2B	5320	16183;16184;16185	chr2:178632978;178632977;178632976	chr2:179497705;179497704;179497703
Novex-1	5445	16558;16559;16560	chr2:178632978;178632977;178632976	chr2:179497705;179497704;179497703
Novex-2	5512	16759;16760;16761	chr2:178632978;178632977;178632976	chr2:179497705;179497704;179497703
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-94
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.2498
• 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
T/K	rs2059984757	None	0.995	N	0.71	0.319	0.280181792013	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/K	rs2059984757	None	0.995	N	0.71	0.319	0.280181792013	gnomAD-4.0.0	2.03011E-06	None	None	None	None	N	None	3.49491E-05	0	None	0	0	None	0	0	0	0	0
T/R	None	None	0.998	N	0.809	0.341	0.323615622048	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	1.26695E-04	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
T/A	0.1684	likely_benign	0.1479	benign	-0.667	Destabilizing	0.921	D	0.587	neutral	N	0.366120779	None	None	N
T/C	0.8172	likely_pathogenic	0.7911	pathogenic	-0.432	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/D	0.5868	likely_pathogenic	0.5812	pathogenic	0.28	Stabilizing	0.996	D	0.71	prob.delet.	None	None	None	None	N
T/E	0.4629	ambiguous	0.442	ambiguous	0.279	Stabilizing	0.996	D	0.721	deleterious	None	None	None	None	N
T/F	0.7783	likely_pathogenic	0.7435	pathogenic	-0.787	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
T/G	0.4567	ambiguous	0.4402	ambiguous	-0.913	Destabilizing	0.987	D	0.668	prob.neutral	None	None	None	None	N
T/H	0.6386	likely_pathogenic	0.6269	pathogenic	-1.141	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/I	0.6911	likely_pathogenic	0.6307	pathogenic	-0.111	Destabilizing	0.998	D	0.806	deleterious	N	0.433552584	None	None	N
T/K	0.493	ambiguous	0.4826	ambiguous	-0.502	Destabilizing	0.995	D	0.71	prob.delet.	N	0.420121309	None	None	N
T/L	0.391	ambiguous	0.3528	ambiguous	-0.111	Destabilizing	0.993	D	0.664	prob.neutral	None	None	None	None	N
T/M	0.2132	likely_benign	0.1894	benign	0.042	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/N	0.229	likely_benign	0.2246	benign	-0.444	Destabilizing	0.996	D	0.699	prob.delet.	None	None	None	None	N
T/P	0.4582	ambiguous	0.4602	ambiguous	-0.263	Destabilizing	0.998	D	0.81	deleterious	N	0.467338848	None	None	N
T/Q	0.4426	ambiguous	0.4243	ambiguous	-0.561	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
T/R	0.3992	ambiguous	0.3985	ambiguous	-0.329	Destabilizing	0.998	D	0.809	deleterious	N	0.429648684	None	None	N
T/S	0.1661	likely_benign	0.1503	benign	-0.779	Destabilizing	0.686	D	0.272	neutral	N	0.392730713	None	None	N
T/V	0.5372	ambiguous	0.4869	ambiguous	-0.263	Destabilizing	0.993	D	0.605	neutral	None	None	None	None	N
T/W	0.9207	likely_pathogenic	0.9139	pathogenic	-0.731	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
T/Y	0.76	likely_pathogenic	0.747	pathogenic	-0.478	Destabilizing	0.999	D	0.812	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.