TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15177	45754;45755;45756	chr2:178621189;178621188;178621187	chr2:179485916;179485915;179485914
N2AB	13536	40831;40832;40833	chr2:178621189;178621188;178621187	chr2:179485916;179485915;179485914
N2A	12609	38050;38051;38052	chr2:178621189;178621188;178621187	chr2:179485916;179485915;179485914
N2B	6112	18559;18560;18561	chr2:178621189;178621188;178621187	chr2:179485916;179485915;179485914
Novex-1	6237	18934;18935;18936	chr2:178621189;178621188;178621187	chr2:179485916;179485915;179485914
Novex-2	6304	19135;19136;19137	chr2:178621189;178621188;178621187	chr2:179485916;179485915;179485914
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-103
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.1449
• 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	rs1298913743	-0.711	0.835	N	0.496	0.227	0.53819168318	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
V/L	rs1298913743	-0.711	0.835	N	0.496	0.227	0.53819168318	gnomAD-4.0.0	1.59379E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88402E-05	0	0	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	0.3081	likely_benign	0.2523	benign	-2.261	Highly Destabilizing	0.91	D	0.561	neutral	D	0.550384142	None	None	N
V/C	0.8729	likely_pathogenic	0.7914	pathogenic	-1.696	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
V/D	0.8271	likely_pathogenic	0.7403	pathogenic	-2.75	Highly Destabilizing	0.994	D	0.737	prob.delet.	D	0.570198778	None	None	N
V/E	0.5731	likely_pathogenic	0.4699	ambiguous	-2.593	Highly Destabilizing	0.996	D	0.7	prob.neutral	None	None	None	None	N
V/F	0.3008	likely_benign	0.2391	benign	-1.383	Destabilizing	0.989	D	0.712	prob.delet.	D	0.537134172	None	None	N
V/G	0.6283	likely_pathogenic	0.5233	ambiguous	-2.734	Highly Destabilizing	0.994	D	0.721	prob.delet.	D	0.673853094	None	None	N
V/H	0.7653	likely_pathogenic	0.6712	pathogenic	-2.36	Highly Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
V/I	0.083	likely_benign	0.0783	benign	-0.961	Destabilizing	0.248	N	0.293	neutral	N	0.478825059	None	None	N
V/K	0.6441	likely_pathogenic	0.5214	ambiguous	-2.023	Highly Destabilizing	0.996	D	0.704	prob.neutral	None	None	None	None	N
V/L	0.2474	likely_benign	0.2164	benign	-0.961	Destabilizing	0.835	D	0.496	neutral	N	0.50912196	None	None	N
V/M	0.2109	likely_benign	0.1779	benign	-0.879	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	N
V/N	0.6313	likely_pathogenic	0.546	ambiguous	-2.162	Highly Destabilizing	0.996	D	0.757	deleterious	None	None	None	None	N
V/P	0.9901	likely_pathogenic	0.9848	pathogenic	-1.367	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
V/Q	0.5402	ambiguous	0.4474	ambiguous	-2.112	Highly Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
V/R	0.538	ambiguous	0.4195	ambiguous	-1.639	Destabilizing	0.996	D	0.764	deleterious	None	None	None	None	N
V/S	0.4549	ambiguous	0.3665	ambiguous	-2.748	Highly Destabilizing	0.983	D	0.683	prob.neutral	None	None	None	None	N
V/T	0.2861	likely_benign	0.2236	benign	-2.472	Highly Destabilizing	0.503	D	0.459	neutral	None	None	None	None	N
V/W	0.9293	likely_pathogenic	0.8688	pathogenic	-1.842	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
V/Y	0.7581	likely_pathogenic	0.6746	pathogenic	-1.541	Destabilizing	0.999	D	0.717	prob.delet.	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.