TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17689	53290;53291;53292	chr2:178607623;178607622;178607621	chr2:179472350;179472349;179472348
N2AB	16048	48367;48368;48369	chr2:178607623;178607622;178607621	chr2:179472350;179472349;179472348
N2A	15121	45586;45587;45588	chr2:178607623;178607622;178607621	chr2:179472350;179472349;179472348
N2B	8624	26095;26096;26097	chr2:178607623;178607622;178607621	chr2:179472350;179472349;179472348
Novex-1	8749	26470;26471;26472	chr2:178607623;178607622;178607621	chr2:179472350;179472349;179472348
Novex-2	8816	26671;26672;26673	chr2:178607623;178607622;178607621	chr2:179472350;179472349;179472348
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-113
• Domain position: 13
• Structural Position: 26
• Q(SASA): 0.3439
• 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/A	None	None	0.91	N	0.478	0.142	0.154104182512	gnomAD-4.0.0	6.00164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56254E-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	0.1462	likely_benign	0.1415	benign	-0.668	Destabilizing	0.91	D	0.478	neutral	N	0.455238042	None	None	N
T/C	0.6044	likely_pathogenic	0.5791	pathogenic	-0.478	Destabilizing	1.0	D	0.517	neutral	None	None	None	None	N
T/D	0.455	ambiguous	0.4584	ambiguous	0.12	Stabilizing	0.999	D	0.495	neutral	None	None	None	None	N
T/E	0.371	ambiguous	0.4036	ambiguous	0.149	Stabilizing	0.999	D	0.473	neutral	None	None	None	None	N
T/F	0.4965	ambiguous	0.4732	ambiguous	-0.692	Destabilizing	0.991	D	0.587	neutral	None	None	None	None	N
T/G	0.5269	ambiguous	0.5073	ambiguous	-0.946	Destabilizing	0.996	D	0.513	neutral	None	None	None	None	N
T/H	0.4747	ambiguous	0.468	ambiguous	-1.135	Destabilizing	1.0	D	0.568	neutral	None	None	None	None	N
T/I	0.2173	likely_benign	0.2057	benign	-0.018	Destabilizing	0.248	N	0.257	neutral	N	0.471229156	None	None	N
T/K	0.4173	ambiguous	0.4315	ambiguous	-0.555	Destabilizing	0.996	D	0.465	neutral	None	None	None	None	N
T/L	0.1727	likely_benign	0.164	benign	-0.018	Destabilizing	0.871	D	0.444	neutral	None	None	None	None	N
T/M	0.1088	likely_benign	0.1048	benign	0.021	Stabilizing	0.871	D	0.427	neutral	None	None	None	None	N
T/N	0.1735	likely_benign	0.1553	benign	-0.602	Destabilizing	0.998	D	0.481	neutral	N	0.488243534	None	None	N
T/P	0.1719	likely_benign	0.1514	benign	-0.201	Destabilizing	0.998	D	0.499	neutral	N	0.472620721	None	None	N
T/Q	0.3549	ambiguous	0.3631	ambiguous	-0.645	Destabilizing	0.996	D	0.503	neutral	None	None	None	None	N
T/R	0.4027	ambiguous	0.4125	ambiguous	-0.417	Destabilizing	0.996	D	0.507	neutral	None	None	None	None	N
T/S	0.1797	likely_benign	0.1673	benign	-0.904	Destabilizing	0.98	D	0.454	neutral	N	0.453013453	None	None	N
T/V	0.1674	likely_benign	0.162	benign	-0.201	Destabilizing	0.304	N	0.219	neutral	None	None	None	None	N
T/W	0.7984	likely_pathogenic	0.7984	pathogenic	-0.681	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
T/Y	0.4677	ambiguous	0.4657	ambiguous	-0.411	Destabilizing	0.999	D	0.579	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.