TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21511	64756;64757;64758	chr2:178585213;178585212;178585211	chr2:179449940;179449939;179449938
N2AB	19870	59833;59834;59835	chr2:178585213;178585212;178585211	chr2:179449940;179449939;179449938
N2A	18943	57052;57053;57054	chr2:178585213;178585212;178585211	chr2:179449940;179449939;179449938
N2B	12446	37561;37562;37563	chr2:178585213;178585212;178585211	chr2:179449940;179449939;179449938
Novex-1	12571	37936;37937;37938	chr2:178585213;178585212;178585211	chr2:179449940;179449939;179449938
Novex-2	12638	38137;38138;38139	chr2:178585213;178585212;178585211	chr2:179449940;179449939;179449938
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-124
• Domain position: 43
• Structural Position: 109
• Q(SASA): 0.8076
• 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
S/R	None	None	0.976	N	0.358	0.266	0.262662153117	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0945	likely_benign	0.0865	benign	-0.126	Destabilizing	0.863	D	0.363	neutral	None	None	None	None	I
S/C	0.2176	likely_benign	0.1741	benign	-0.257	Destabilizing	0.999	D	0.393	neutral	N	0.470646498	None	None	I
S/D	0.4901	ambiguous	0.3822	ambiguous	-0.051	Destabilizing	0.02	N	0.136	neutral	None	None	None	None	I
S/E	0.6054	likely_pathogenic	0.5025	ambiguous	-0.16	Destabilizing	0.17	N	0.17	neutral	None	None	None	None	I
S/F	0.3679	ambiguous	0.3054	benign	-0.861	Destabilizing	0.997	D	0.408	neutral	None	None	None	None	I
S/G	0.1125	likely_benign	0.1011	benign	-0.178	Destabilizing	0.826	D	0.345	neutral	N	0.455090966	None	None	I
S/H	0.4671	ambiguous	0.3726	ambiguous	-0.537	Destabilizing	0.997	D	0.349	neutral	None	None	None	None	I
S/I	0.2695	likely_benign	0.2235	benign	-0.121	Destabilizing	0.996	D	0.421	neutral	N	0.481749314	None	None	I
S/K	0.7722	likely_pathogenic	0.6484	pathogenic	-0.381	Destabilizing	0.939	D	0.312	neutral	None	None	None	None	I
S/L	0.136	likely_benign	0.1191	benign	-0.121	Destabilizing	0.969	D	0.411	neutral	None	None	None	None	I
S/M	0.272	likely_benign	0.2427	benign	-0.077	Destabilizing	0.999	D	0.355	neutral	None	None	None	None	I
S/N	0.1728	likely_benign	0.1488	benign	-0.064	Destabilizing	0.92	D	0.336	neutral	N	0.480701487	None	None	I
S/P	0.1433	likely_benign	0.1127	benign	-0.098	Destabilizing	0.997	D	0.355	neutral	None	None	None	None	I
S/Q	0.5651	likely_pathogenic	0.4822	ambiguous	-0.305	Destabilizing	0.939	D	0.329	neutral	None	None	None	None	I
S/R	0.7444	likely_pathogenic	0.6239	pathogenic	-0.118	Destabilizing	0.976	D	0.358	neutral	N	0.452053448	None	None	I
S/T	0.0966	likely_benign	0.0869	benign	-0.163	Destabilizing	0.959	D	0.357	neutral	N	0.49091848	None	None	I
S/V	0.2477	likely_benign	0.2064	benign	-0.098	Destabilizing	0.969	D	0.429	neutral	None	None	None	None	I
S/W	0.5359	ambiguous	0.448	ambiguous	-0.957	Destabilizing	0.999	D	0.51	neutral	None	None	None	None	I
S/Y	0.3354	likely_benign	0.2723	benign	-0.637	Destabilizing	0.997	D	0.407	neutral	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.