TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15708	47347;47348;47349	chr2:178618336;178618335;178618334	chr2:179483063;179483062;179483061
N2AB	14067	42424;42425;42426	chr2:178618336;178618335;178618334	chr2:179483063;179483062;179483061
N2A	13140	39643;39644;39645	chr2:178618336;178618335;178618334	chr2:179483063;179483062;179483061
N2B	6643	20152;20153;20154	chr2:178618336;178618335;178618334	chr2:179483063;179483062;179483061
Novex-1	6768	20527;20528;20529	chr2:178618336;178618335;178618334	chr2:179483063;179483062;179483061
Novex-2	6835	20728;20729;20730	chr2:178618336;178618335;178618334	chr2:179483063;179483062;179483061
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-1
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1433
• 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/A	None	None	0.996	N	0.481	0.361	0.282179105231	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
T/R	rs1553711574	None	1.0	N	0.751	0.393	0.500994481783	gnomAD-4.0.0	6.84625E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99896E-07	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	0.186	likely_benign	0.1621	benign	-0.988	Destabilizing	0.996	D	0.481	neutral	N	0.457647567	None	None	N
T/C	0.6976	likely_pathogenic	0.6133	pathogenic	-0.511	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
T/D	0.7346	likely_pathogenic	0.6654	pathogenic	-0.191	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
T/E	0.7695	likely_pathogenic	0.6963	pathogenic	-0.11	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/F	0.8347	likely_pathogenic	0.7771	pathogenic	-0.917	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/G	0.4127	ambiguous	0.3924	ambiguous	-1.32	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
T/H	0.7477	likely_pathogenic	0.6955	pathogenic	-1.468	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
T/I	0.7463	likely_pathogenic	0.6757	pathogenic	-0.166	Destabilizing	0.992	D	0.579	neutral	N	0.502158545	None	None	N
T/K	0.7267	likely_pathogenic	0.6499	pathogenic	-0.545	Destabilizing	1.0	D	0.708	prob.delet.	N	0.481881848	None	None	N
T/L	0.4584	ambiguous	0.4118	ambiguous	-0.166	Destabilizing	0.994	D	0.461	neutral	None	None	None	None	N
T/M	0.2958	likely_benign	0.2826	benign	-0.005	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
T/N	0.3916	ambiguous	0.3238	benign	-0.767	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
T/P	0.8573	likely_pathogenic	0.8032	pathogenic	-0.407	Destabilizing	1.0	D	0.739	prob.delet.	D	0.535815254	None	None	N
T/Q	0.6623	likely_pathogenic	0.6025	pathogenic	-0.736	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/R	0.6733	likely_pathogenic	0.6063	pathogenic	-0.501	Destabilizing	1.0	D	0.751	deleterious	N	0.484247863	None	None	N
T/S	0.2131	likely_benign	0.1825	benign	-1.102	Destabilizing	0.998	D	0.495	neutral	N	0.468524214	None	None	N
T/V	0.4599	ambiguous	0.3936	ambiguous	-0.407	Destabilizing	0.813	D	0.35	neutral	None	None	None	None	N
T/W	0.9562	likely_pathogenic	0.9393	pathogenic	-0.9	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/Y	0.8692	likely_pathogenic	0.821	pathogenic	-0.617	Destabilizing	1.0	D	0.759	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.