TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35304	106135;106136;106137	chr2:178530705;178530704;178530703	chr2:179395432;179395431;179395430
N2AB	33663	101212;101213;101214	chr2:178530705;178530704;178530703	chr2:179395432;179395431;179395430
N2A	32736	98431;98432;98433	chr2:178530705;178530704;178530703	chr2:179395432;179395431;179395430
N2B	26239	78940;78941;78942	chr2:178530705;178530704;178530703	chr2:179395432;179395431;179395430
Novex-1	26364	79315;79316;79317	chr2:178530705;178530704;178530703	chr2:179395432;179395431;179395430
Novex-2	26431	79516;79517;79518	chr2:178530705;178530704;178530703	chr2:179395432;179395431;179395430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-165
• Domain position: 19
• Structural Position: 31
• Q(SASA): 0.274
• 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/N	None	None	0.213	N	0.39	0.079	0.378148810121	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
T/A	0.1198	likely_benign	0.1189	benign	-1.043	Destabilizing	0.047	N	0.372	neutral	D	0.523111909	None	None	N
T/C	0.4968	ambiguous	0.5533	ambiguous	-0.819	Destabilizing	0.002	N	0.403	neutral	None	None	None	None	N
T/D	0.5879	likely_pathogenic	0.5767	pathogenic	-1.307	Destabilizing	0.418	N	0.457	neutral	None	None	None	None	N
T/E	0.4506	ambiguous	0.4478	ambiguous	-1.187	Destabilizing	0.228	N	0.435	neutral	None	None	None	None	N
T/F	0.2766	likely_benign	0.2851	benign	-0.757	Destabilizing	0.002	N	0.391	neutral	None	None	None	None	N
T/G	0.3828	ambiguous	0.3952	ambiguous	-1.411	Destabilizing	0.129	N	0.439	neutral	None	None	None	None	N
T/H	0.2866	likely_benign	0.2931	benign	-1.609	Destabilizing	0.002	N	0.465	neutral	None	None	None	None	N
T/I	0.1695	likely_benign	0.1778	benign	-0.111	Destabilizing	0.007	N	0.273	neutral	N	0.489241636	None	None	N
T/K	0.2496	likely_benign	0.2409	benign	-0.798	Destabilizing	0.418	N	0.455	neutral	None	None	None	None	N
T/L	0.1419	likely_benign	0.1463	benign	-0.111	Destabilizing	0.061	N	0.411	neutral	None	None	None	None	N
T/M	0.1376	likely_benign	0.1377	benign	0.027	Stabilizing	0.836	D	0.514	neutral	None	None	None	None	N
T/N	0.1744	likely_benign	0.1734	benign	-1.194	Destabilizing	0.213	N	0.39	neutral	N	0.501408486	None	None	N
T/P	0.5512	ambiguous	0.4855	ambiguous	-0.389	Destabilizing	0.523	D	0.535	neutral	N	0.50987604	None	None	N
T/Q	0.2882	likely_benign	0.286	benign	-1.168	Destabilizing	0.418	N	0.579	neutral	None	None	None	None	N
T/R	0.1897	likely_benign	0.1795	benign	-0.779	Destabilizing	0.418	N	0.526	neutral	None	None	None	None	N
T/S	0.1314	likely_benign	0.1349	benign	-1.402	Destabilizing	0.001	N	0.193	neutral	N	0.472587088	None	None	N
T/V	0.186	likely_benign	0.1973	benign	-0.389	Destabilizing	0.129	N	0.365	neutral	None	None	None	None	N
T/W	0.6932	likely_pathogenic	0.6951	pathogenic	-0.82	Destabilizing	0.983	D	0.549	neutral	None	None	None	None	N
T/Y	0.3633	ambiguous	0.3622	ambiguous	-0.509	Destabilizing	0.264	N	0.509	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.