TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28038	84337;84338;84339	chr2:178562020;178562019;178562018	chr2:179426747;179426746;179426745
N2AB	26397	79414;79415;79416	chr2:178562020;178562019;178562018	chr2:179426747;179426746;179426745
N2A	25470	76633;76634;76635	chr2:178562020;178562019;178562018	chr2:179426747;179426746;179426745
N2B	18973	57142;57143;57144	chr2:178562020;178562019;178562018	chr2:179426747;179426746;179426745
Novex-1	19098	57517;57518;57519	chr2:178562020;178562019;178562018	chr2:179426747;179426746;179426745
Novex-2	19165	57718;57719;57720	chr2:178562020;178562019;178562018	chr2:179426747;179426746;179426745
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-142
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.4196
• 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	0.698	D	0.605	0.381	0.60194832725	gnomAD-4.0.0	6.84367E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99535E-07	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	0.0853	likely_benign	0.0826	benign	-0.594	Destabilizing	0.489	N	0.375	neutral	N	0.466565193	None	None	I
S/C	0.1174	likely_benign	0.1142	benign	-0.496	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	I
S/D	0.4183	ambiguous	0.4004	ambiguous	-0.786	Destabilizing	0.86	D	0.407	neutral	None	None	None	None	I
S/E	0.4082	ambiguous	0.3936	ambiguous	-0.845	Destabilizing	0.86	D	0.404	neutral	None	None	None	None	I
S/F	0.1867	likely_benign	0.1864	benign	-1.152	Destabilizing	0.978	D	0.665	neutral	None	None	None	None	I
S/G	0.1335	likely_benign	0.1276	benign	-0.745	Destabilizing	0.86	D	0.393	neutral	None	None	None	None	I
S/H	0.2946	likely_benign	0.2803	benign	-1.348	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	I
S/I	0.1909	likely_benign	0.1781	benign	-0.31	Destabilizing	0.956	D	0.61	neutral	None	None	None	None	I
S/K	0.5609	ambiguous	0.5368	ambiguous	-0.682	Destabilizing	0.86	D	0.402	neutral	None	None	None	None	I
S/L	0.1114	likely_benign	0.1123	benign	-0.31	Destabilizing	0.698	D	0.605	neutral	D	0.531037959	None	None	I
S/M	0.1887	likely_benign	0.1804	benign	0.197	Stabilizing	0.998	D	0.555	neutral	None	None	None	None	I
S/N	0.1496	likely_benign	0.14	benign	-0.619	Destabilizing	0.86	D	0.427	neutral	None	None	None	None	I
S/P	0.9197	likely_pathogenic	0.9198	pathogenic	-0.376	Destabilizing	0.97	D	0.505	neutral	N	0.504116661	None	None	I
S/Q	0.38	ambiguous	0.3661	ambiguous	-0.975	Destabilizing	0.978	D	0.499	neutral	None	None	None	None	I
S/R	0.4771	ambiguous	0.4628	ambiguous	-0.402	Destabilizing	0.956	D	0.513	neutral	None	None	None	None	I
S/T	0.0716	likely_benign	0.0682	benign	-0.623	Destabilizing	0.002	N	0.189	neutral	N	0.392219363	None	None	I
S/V	0.1813	likely_benign	0.1681	benign	-0.376	Destabilizing	0.754	D	0.597	neutral	None	None	None	None	I
S/W	0.3479	ambiguous	0.3537	ambiguous	-1.123	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	I
S/Y	0.1899	likely_benign	0.183	benign	-0.835	Destabilizing	0.993	D	0.671	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.