TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22540	67843;67844;67845	chr2:178579579;178579578;178579577	chr2:179444306;179444305;179444304
N2AB	20899	62920;62921;62922	chr2:178579579;178579578;178579577	chr2:179444306;179444305;179444304
N2A	19972	60139;60140;60141	chr2:178579579;178579578;178579577	chr2:179444306;179444305;179444304
N2B	13475	40648;40649;40650	chr2:178579579;178579578;178579577	chr2:179444306;179444305;179444304
Novex-1	13600	41023;41024;41025	chr2:178579579;178579578;178579577	chr2:179444306;179444305;179444304
Novex-2	13667	41224;41225;41226	chr2:178579579;178579578;178579577	chr2:179444306;179444305;179444304
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-51
• Domain position: 90
• Structural Position: 129
• Q(SASA): 0.4077
• 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/L	None	None	None	N	0.186	0.063	0.277730125212	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
V/A	0.1357	likely_benign	0.155	benign	-1.146	Destabilizing	0.026	N	0.553	neutral	N	0.506376296	None	None	N
V/C	0.6553	likely_pathogenic	0.6798	pathogenic	-0.866	Destabilizing	0.934	D	0.697	prob.delet.	None	None	None	None	N
V/D	0.3253	likely_benign	0.3611	ambiguous	-0.841	Destabilizing	0.552	D	0.739	deleterious	None	None	None	None	N
V/E	0.2043	likely_benign	0.233	benign	-0.881	Destabilizing	0.481	N	0.669	prob.neutral	N	0.507936521	None	None	N
V/F	0.1317	likely_benign	0.1497	benign	-0.921	Destabilizing	0.233	N	0.65	prob.neutral	None	None	None	None	N
V/G	0.2382	likely_benign	0.2663	benign	-1.408	Destabilizing	0.314	N	0.646	neutral	N	0.507936521	None	None	N
V/H	0.4123	ambiguous	0.4506	ambiguous	-0.87	Destabilizing	0.934	D	0.8	deleterious	None	None	None	None	N
V/I	0.0733	likely_benign	0.076	benign	-0.556	Destabilizing	0.034	N	0.55	neutral	None	None	None	None	N
V/K	0.2129	likely_benign	0.2439	benign	-1.025	Destabilizing	0.378	N	0.587	neutral	None	None	None	None	N
V/L	0.1138	likely_benign	0.1307	benign	-0.556	Destabilizing	None	N	0.186	neutral	N	0.405289369	None	None	N
V/M	0.1007	likely_benign	0.1122	benign	-0.485	Destabilizing	0.004	N	0.335	neutral	N	0.445983985	None	None	N
V/N	0.2515	likely_benign	0.2669	benign	-0.802	Destabilizing	0.552	D	0.76	deleterious	None	None	None	None	N
V/P	0.5188	ambiguous	0.591	pathogenic	-0.717	Destabilizing	0.789	D	0.717	prob.delet.	None	None	None	None	N
V/Q	0.2161	likely_benign	0.2473	benign	-1.0	Destabilizing	0.378	N	0.709	prob.delet.	None	None	None	None	N
V/R	0.1871	likely_benign	0.217	benign	-0.463	Destabilizing	0.378	N	0.74	deleterious	None	None	None	None	N
V/S	0.1762	likely_benign	0.1881	benign	-1.279	Destabilizing	0.378	N	0.582	neutral	None	None	None	None	N
V/T	0.1083	likely_benign	0.1127	benign	-1.212	Destabilizing	0.147	N	0.611	neutral	None	None	None	None	N
V/W	0.6343	likely_pathogenic	0.7186	pathogenic	-1.046	Destabilizing	0.934	D	0.813	deleterious	None	None	None	None	N
V/Y	0.4367	ambiguous	0.4824	ambiguous	-0.771	Destabilizing	0.552	D	0.648	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.