TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15864	47815;47816;47817	chr2:178617495;178617494;178617493	chr2:179482222;179482221;179482220
N2AB	14223	42892;42893;42894	chr2:178617495;178617494;178617493	chr2:179482222;179482221;179482220
N2A	13296	40111;40112;40113	chr2:178617495;178617494;178617493	chr2:179482222;179482221;179482220
N2B	6799	20620;20621;20622	chr2:178617495;178617494;178617493	chr2:179482222;179482221;179482220
Novex-1	6924	20995;20996;20997	chr2:178617495;178617494;178617493	chr2:179482222;179482221;179482220
Novex-2	6991	21196;21197;21198	chr2:178617495;178617494;178617493	chr2:179482222;179482221;179482220
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-3
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2301
• 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
V/I	rs1553709304	None	None	N	0.116	0.039	0.156986980423	gnomAD-4.0.0	1.65486E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91596E-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	0.158	likely_benign	0.1849	benign	-1.556	Destabilizing	0.081	N	0.327	neutral	N	0.448005181	None	None	N
V/C	0.5483	ambiguous	0.6249	pathogenic	-0.916	Destabilizing	0.859	D	0.561	neutral	None	None	None	None	N
V/D	0.3853	ambiguous	0.424	ambiguous	-1.642	Destabilizing	0.22	N	0.648	neutral	None	None	None	None	N
V/E	0.2434	likely_benign	0.2471	benign	-1.653	Destabilizing	0.096	N	0.589	neutral	N	0.424778467	None	None	N
V/F	0.1378	likely_benign	0.1877	benign	-1.219	Destabilizing	0.497	N	0.614	neutral	None	None	None	None	N
V/G	0.1686	likely_benign	0.1932	benign	-1.865	Destabilizing	0.301	N	0.596	neutral	N	0.435049012	None	None	N
V/H	0.4454	ambiguous	0.5158	ambiguous	-1.492	Destabilizing	0.883	D	0.592	neutral	None	None	None	None	N
V/I	0.0649	likely_benign	0.0753	benign	-0.804	Destabilizing	None	N	0.116	neutral	N	0.439889809	None	None	N
V/K	0.2405	likely_benign	0.2521	benign	-1.423	Destabilizing	0.124	N	0.585	neutral	None	None	None	None	N
V/L	0.0982	likely_benign	0.1243	benign	-0.804	Destabilizing	None	N	0.139	neutral	N	0.396407843	None	None	N
V/M	0.1046	likely_benign	0.1298	benign	-0.52	Destabilizing	0.497	N	0.527	neutral	None	None	None	None	N
V/N	0.211	likely_benign	0.25	benign	-1.14	Destabilizing	0.667	D	0.641	neutral	None	None	None	None	N
V/P	0.7076	likely_pathogenic	0.7337	pathogenic	-1.021	Destabilizing	0.859	D	0.635	neutral	None	None	None	None	N
V/Q	0.2171	likely_benign	0.2197	benign	-1.336	Destabilizing	0.011	N	0.458	neutral	None	None	None	None	N
V/R	0.1947	likely_benign	0.2047	benign	-0.848	Destabilizing	0.497	N	0.645	neutral	None	None	None	None	N
V/S	0.1768	likely_benign	0.2012	benign	-1.586	Destabilizing	0.124	N	0.555	neutral	None	None	None	None	N
V/T	0.1468	likely_benign	0.1546	benign	-1.501	Destabilizing	0.004	N	0.16	neutral	None	None	None	None	N
V/W	0.6623	likely_pathogenic	0.7624	pathogenic	-1.434	Destabilizing	0.958	D	0.615	neutral	None	None	None	None	N
V/Y	0.3983	ambiguous	0.4878	ambiguous	-1.178	Destabilizing	0.667	D	0.609	neutral	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.