TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21971	66136;66137;66138	chr2:178582545;178582544;178582543	chr2:179447272;179447271;179447270
N2AB	20330	61213;61214;61215	chr2:178582545;178582544;178582543	chr2:179447272;179447271;179447270
N2A	19403	58432;58433;58434	chr2:178582545;178582544;178582543	chr2:179447272;179447271;179447270
N2B	12906	38941;38942;38943	chr2:178582545;178582544;178582543	chr2:179447272;179447271;179447270
Novex-1	13031	39316;39317;39318	chr2:178582545;178582544;178582543	chr2:179447272;179447271;179447270
Novex-2	13098	39517;39518;39519	chr2:178582545;178582544;178582543	chr2:179447272;179447271;179447270
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-47
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4256
• 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
D/E	rs1313945258	None	0.979	N	0.414	0.199	0.293147016451	gnomAD-4.0.0	6.84795E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.6581E-05
D/N	None	None	0.998	N	0.679	0.324	0.306053231325	gnomAD-4.0.0	1.59448E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86402E-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
D/A	0.8274	likely_pathogenic	0.7306	pathogenic	-0.833	Destabilizing	0.919	D	0.649	neutral	N	0.467711935	None	None	N
D/C	0.9606	likely_pathogenic	0.9293	pathogenic	-0.326	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
D/E	0.4967	ambiguous	0.4368	ambiguous	-0.874	Destabilizing	0.979	D	0.414	neutral	N	0.443695829	None	None	N
D/F	0.9579	likely_pathogenic	0.9438	pathogenic	-0.828	Destabilizing	0.991	D	0.761	deleterious	None	None	None	None	N
D/G	0.6906	likely_pathogenic	0.5796	pathogenic	-1.123	Destabilizing	0.979	D	0.688	prob.neutral	N	0.474282074	None	None	N
D/H	0.8486	likely_pathogenic	0.7812	pathogenic	-1.08	Destabilizing	0.999	D	0.698	prob.neutral	N	0.46952236	None	None	N
D/I	0.9474	likely_pathogenic	0.9151	pathogenic	-0.075	Destabilizing	0.982	D	0.741	deleterious	None	None	None	None	N
D/K	0.9397	likely_pathogenic	0.9087	pathogenic	-0.382	Destabilizing	0.995	D	0.779	deleterious	None	None	None	None	N
D/L	0.9257	likely_pathogenic	0.8943	pathogenic	-0.075	Destabilizing	0.982	D	0.739	prob.delet.	None	None	None	None	N
D/M	0.9628	likely_pathogenic	0.945	pathogenic	0.444	Stabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
D/N	0.2864	likely_benign	0.243	benign	-0.691	Destabilizing	0.998	D	0.679	prob.neutral	N	0.473130514	None	None	N
D/P	0.9899	likely_pathogenic	0.9843	pathogenic	-0.305	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
D/Q	0.8581	likely_pathogenic	0.8001	pathogenic	-0.651	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
D/R	0.9359	likely_pathogenic	0.9045	pathogenic	-0.327	Destabilizing	0.995	D	0.769	deleterious	None	None	None	None	N
D/S	0.5187	ambiguous	0.4059	ambiguous	-0.959	Destabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	N
D/T	0.6919	likely_pathogenic	0.5818	pathogenic	-0.717	Destabilizing	0.991	D	0.736	prob.delet.	None	None	None	None	N
D/V	0.8777	likely_pathogenic	0.8093	pathogenic	-0.305	Destabilizing	0.142	N	0.471	neutral	N	0.50598436	None	None	N
D/W	0.9893	likely_pathogenic	0.984	pathogenic	-0.687	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
D/Y	0.8185	likely_pathogenic	0.7441	pathogenic	-0.58	Destabilizing	0.998	D	0.757	deleterious	N	0.50573087	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.