TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9468	28627;28628;28629	chr2:178710695;178710694;178710693	chr2:179575422;179575421;179575420
N2AB	9151	27676;27677;27678	chr2:178710695;178710694;178710693	chr2:179575422;179575421;179575420
N2A	8224	24895;24896;24897	chr2:178710695;178710694;178710693	chr2:179575422;179575421;179575420
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-80
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1087
• 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/I	None	None	0.317	None	0.735	0.186	0.442977140156	gnomAD-4.0.0	1.59206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85804E-06	0	0
T/S	rs1241585388	None	None	None	0.271	0.044	0.17258766438	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
T/S	rs1241585388	None	None	None	0.271	0.044	0.17258766438	gnomAD-4.0.0	1.31413E-05	None	None	None	None	N	None	4.82509E-05	0	None	0	0	None	0	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
T/A	0.0958	likely_benign	0.1235	benign	-1.159	Destabilizing	0.027	N	0.649	neutral	None	None	None	None	N
T/C	0.5386	ambiguous	0.6162	pathogenic	-0.714	Destabilizing	0.824	D	0.669	neutral	None	None	None	None	N
T/D	0.5271	ambiguous	0.689	pathogenic	-1.427	Destabilizing	0.081	N	0.721	prob.delet.	None	None	None	None	N
T/E	0.4572	ambiguous	0.5153	ambiguous	-1.213	Destabilizing	0.081	N	0.724	prob.delet.	None	None	None	None	N
T/F	0.2798	likely_benign	0.3359	benign	-0.846	Destabilizing	0.001	N	0.67	neutral	None	None	None	None	N
T/G	0.3226	likely_benign	0.5072	ambiguous	-1.582	Destabilizing	0.081	N	0.713	prob.delet.	None	None	None	None	N
T/H	0.2842	likely_benign	0.3713	ambiguous	-1.666	Destabilizing	0.824	D	0.698	prob.neutral	None	None	None	None	N
T/I	0.1946	likely_benign	0.1904	benign	-0.039	Destabilizing	0.317	N	0.735	prob.delet.	None	None	None	None	N
T/K	0.2797	likely_benign	0.3565	ambiguous	-0.277	Destabilizing	0.081	N	0.725	prob.delet.	None	None	None	None	N
T/L	0.1461	likely_benign	0.169	benign	-0.039	Destabilizing	0.081	N	0.713	prob.delet.	None	None	None	None	N
T/M	0.1314	likely_benign	0.1294	benign	-0.039	Destabilizing	0.935	D	0.683	prob.neutral	None	None	None	None	N
T/N	0.1645	likely_benign	0.2509	benign	-1.022	Destabilizing	0.062	N	0.691	prob.neutral	None	None	None	None	N
T/P	0.7083	likely_pathogenic	0.8531	pathogenic	-0.382	Destabilizing	0.001	N	0.577	neutral	None	None	None	None	N
T/Q	0.2848	likely_benign	0.352	ambiguous	-0.78	Destabilizing	0.38	N	0.712	prob.delet.	None	None	None	None	N
T/R	0.1926	likely_benign	0.2417	benign	-0.561	Destabilizing	0.38	N	0.713	prob.delet.	None	None	None	None	N
T/S	0.1163	likely_benign	0.1568	benign	-1.267	Destabilizing	None	N	0.271	neutral	None	None	None	None	N
T/V	0.1676	likely_benign	0.1729	benign	-0.382	Destabilizing	0.149	N	0.685	prob.neutral	None	None	None	None	N
T/W	0.6976	likely_pathogenic	0.7621	pathogenic	-0.998	Destabilizing	0.935	D	0.709	prob.delet.	None	None	None	None	N
T/Y	0.3244	likely_benign	0.433	ambiguous	-0.602	Destabilizing	0.235	N	0.714	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.