TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6343	19252;19253;19254	chr2:178729011;178729010;178729009	chr2:179593738;179593737;179593736
N2AB	6026	18301;18302;18303	chr2:178729011;178729010;178729009	chr2:179593738;179593737;179593736
N2A	5099	15520;15521;15522	chr2:178729011;178729010;178729009	chr2:179593738;179593737;179593736
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-47
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4322
• 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
V/A	None	None	None	N	0.075	0.129	0.486209434461	gnomAD-4.0.0	1.59318E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86056E-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
V/A	0.0828	likely_benign	0.0801	benign	-0.431	Destabilizing	None	N	0.075	neutral	N	0.464351607	None	None	I
V/C	0.6018	likely_pathogenic	0.5825	pathogenic	-0.761	Destabilizing	0.864	D	0.323	neutral	None	None	None	None	I
V/D	0.1363	likely_benign	0.1248	benign	0.227	Stabilizing	0.016	N	0.329	neutral	None	None	None	None	I
V/E	0.1077	likely_benign	0.095	benign	0.14	Stabilizing	None	N	0.167	neutral	N	0.364224685	None	None	I
V/F	0.1138	likely_benign	0.1089	benign	-0.513	Destabilizing	0.628	D	0.365	neutral	None	None	None	None	I
V/G	0.1165	likely_benign	0.1169	benign	-0.565	Destabilizing	0.024	N	0.311	neutral	N	0.463602246	None	None	I
V/H	0.2319	likely_benign	0.2221	benign	-0.033	Destabilizing	0.356	N	0.42	neutral	None	None	None	None	I
V/I	0.0753	likely_benign	0.0728	benign	-0.221	Destabilizing	0.061	N	0.219	neutral	None	None	None	None	I
V/K	0.1032	likely_benign	0.1042	benign	-0.309	Destabilizing	0.016	N	0.279	neutral	None	None	None	None	I
V/L	0.1296	likely_benign	0.126	benign	-0.221	Destabilizing	0.024	N	0.223	neutral	N	0.446997998	None	None	I
V/M	0.1008	likely_benign	0.0961	benign	-0.436	Destabilizing	0.56	D	0.295	neutral	D	0.524381346	None	None	I
V/N	0.1194	likely_benign	0.1145	benign	-0.181	Destabilizing	0.072	N	0.407	neutral	None	None	None	None	I
V/P	0.4726	ambiguous	0.5481	ambiguous	-0.257	Destabilizing	0.136	N	0.394	neutral	None	None	None	None	I
V/Q	0.1188	likely_benign	0.1093	benign	-0.333	Destabilizing	0.038	N	0.35	neutral	None	None	None	None	I
V/R	0.0992	likely_benign	0.1041	benign	0.107	Stabilizing	0.038	N	0.41	neutral	None	None	None	None	I
V/S	0.0892	likely_benign	0.0887	benign	-0.626	Destabilizing	0.016	N	0.305	neutral	None	None	None	None	I
V/T	0.0808	likely_benign	0.0777	benign	-0.602	Destabilizing	0.031	N	0.158	neutral	None	None	None	None	I
V/W	0.5565	ambiguous	0.5474	ambiguous	-0.585	Destabilizing	0.864	D	0.435	neutral	None	None	None	None	I
V/Y	0.3376	likely_benign	0.3306	benign	-0.3	Destabilizing	0.628	D	0.362	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.