TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4855	14788;14789;14790	chr2:178735883;178735882;178735881	chr2:179600610;179600609;179600608
N2AB	4538	13837;13838;13839	chr2:178735883;178735882;178735881	chr2:179600610;179600609;179600608
N2A	3611	11056;11057;11058	chr2:178735883;178735882;178735881	chr2:179600610;179600609;179600608
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-31
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.2983
• 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/L	None	None	0.001	N	0.209	0.168	0.460526725402	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62502E-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	0.0841	likely_benign	0.0755	benign	-0.665	Destabilizing	0.047	N	0.209	neutral	N	0.505380109	None	None	I
S/C	0.1261	likely_benign	0.1081	benign	-0.408	Destabilizing	0.983	D	0.394	neutral	None	None	None	None	I
S/D	0.3592	ambiguous	0.2858	benign	-0.154	Destabilizing	0.593	D	0.241	neutral	None	None	None	None	I
S/E	0.3797	ambiguous	0.3193	benign	-0.221	Destabilizing	0.418	N	0.248	neutral	None	None	None	None	I
S/F	0.1735	likely_benign	0.1301	benign	-1.138	Destabilizing	0.557	D	0.477	neutral	None	None	None	None	I
S/G	0.1212	likely_benign	0.1036	benign	-0.823	Destabilizing	0.001	N	0.068	neutral	None	None	None	None	I
S/H	0.254	likely_benign	0.2055	benign	-1.383	Destabilizing	0.94	D	0.407	neutral	None	None	None	None	I
S/I	0.1803	likely_benign	0.141	benign	-0.363	Destabilizing	0.264	N	0.456	neutral	None	None	None	None	I
S/K	0.4728	ambiguous	0.3782	ambiguous	-0.609	Destabilizing	0.004	N	0.077	neutral	None	None	None	None	I
S/L	0.0908	likely_benign	0.0778	benign	-0.363	Destabilizing	0.001	N	0.209	neutral	N	0.40060698	None	None	I
S/M	0.2193	likely_benign	0.1834	benign	0.068	Stabilizing	0.716	D	0.427	neutral	None	None	None	None	I
S/N	0.1525	likely_benign	0.12	benign	-0.394	Destabilizing	0.593	D	0.266	neutral	None	None	None	None	I
S/P	0.2176	likely_benign	0.205	benign	-0.434	Destabilizing	0.921	D	0.439	neutral	N	0.494493532	None	None	I
S/Q	0.3606	ambiguous	0.3071	benign	-0.693	Destabilizing	0.716	D	0.353	neutral	None	None	None	None	I
S/R	0.3944	ambiguous	0.3104	benign	-0.399	Destabilizing	0.264	N	0.429	neutral	None	None	None	None	I
S/T	0.0925	likely_benign	0.0809	benign	-0.497	Destabilizing	0.183	N	0.292	neutral	N	0.459741873	None	None	I
S/V	0.1879	likely_benign	0.1508	benign	-0.434	Destabilizing	0.002	N	0.26	neutral	None	None	None	None	I
S/W	0.2235	likely_benign	0.1883	benign	-1.071	Destabilizing	0.983	D	0.499	neutral	None	None	None	None	I
S/Y	0.1475	likely_benign	0.1154	benign	-0.817	Destabilizing	0.836	D	0.473	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.