TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22371	67336;67337;67338	chr2:178580176;178580175;178580174	chr2:179444903;179444902;179444901
N2AB	20730	62413;62414;62415	chr2:178580176;178580175;178580174	chr2:179444903;179444902;179444901
N2A	19803	59632;59633;59634	chr2:178580176;178580175;178580174	chr2:179444903;179444902;179444901
N2B	13306	40141;40142;40143	chr2:178580176;178580175;178580174	chr2:179444903;179444902;179444901
Novex-1	13431	40516;40517;40518	chr2:178580176;178580175;178580174	chr2:179444903;179444902;179444901
Novex-2	13498	40717;40718;40719	chr2:178580176;178580175;178580174	chr2:179444903;179444902;179444901
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-50
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1096
• 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
A/V	rs2047373918	None	0.79	N	0.363	0.277	0.220303561663	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
A/V	rs2047373918	None	0.79	N	0.363	0.277	0.220303561663	gnomAD-4.0.0	6.57497E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07125E-04	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
A/C	0.4282	ambiguous	0.4159	ambiguous	-1.26	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
A/D	0.9909	likely_pathogenic	0.9896	pathogenic	-1.901	Destabilizing	1.0	D	0.853	deleterious	N	0.510082055	None	None	N
A/E	0.9833	likely_pathogenic	0.98	pathogenic	-1.678	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
A/F	0.8896	likely_pathogenic	0.8689	pathogenic	-0.656	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
A/G	0.3459	ambiguous	0.314	benign	-1.523	Destabilizing	0.999	D	0.635	neutral	N	0.49872575	None	None	N
A/H	0.989	likely_pathogenic	0.9865	pathogenic	-1.929	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
A/I	0.418	ambiguous	0.3469	ambiguous	0.338	Stabilizing	0.988	D	0.731	prob.delet.	None	None	None	None	N
A/K	0.9944	likely_pathogenic	0.9925	pathogenic	-1.002	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
A/L	0.4674	ambiguous	0.4082	ambiguous	0.338	Stabilizing	0.988	D	0.671	neutral	None	None	None	None	N
A/M	0.6582	likely_pathogenic	0.593	pathogenic	-0.136	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
A/N	0.9682	likely_pathogenic	0.963	pathogenic	-1.364	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
A/P	0.9785	likely_pathogenic	0.9775	pathogenic	-0.07	Destabilizing	1.0	D	0.848	deleterious	N	0.510082055	None	None	N
A/Q	0.9726	likely_pathogenic	0.9656	pathogenic	-1.106	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
A/R	0.982	likely_pathogenic	0.9786	pathogenic	-1.242	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/S	0.318	likely_benign	0.308	benign	-1.854	Destabilizing	0.996	D	0.639	neutral	N	0.480368006	None	None	N
A/T	0.2888	likely_benign	0.2556	benign	-1.482	Destabilizing	0.992	D	0.65	neutral	N	0.48307703	None	None	N
A/V	0.1744	likely_benign	0.1479	benign	-0.07	Destabilizing	0.79	D	0.363	neutral	N	0.360644797	None	None	N
A/W	0.9943	likely_pathogenic	0.9927	pathogenic	-1.362	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/Y	0.9698	likely_pathogenic	0.9641	pathogenic	-0.779	Destabilizing	1.0	D	0.897	deleterious	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.