TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27250	81973;81974;81975	chr2:178564384;178564383;178564382	chr2:179429111;179429110;179429109
N2AB	25609	77050;77051;77052	chr2:178564384;178564383;178564382	chr2:179429111;179429110;179429109
N2A	24682	74269;74270;74271	chr2:178564384;178564383;178564382	chr2:179429111;179429110;179429109
N2B	18185	54778;54779;54780	chr2:178564384;178564383;178564382	chr2:179429111;179429110;179429109
Novex-1	18310	55153;55154;55155	chr2:178564384;178564383;178564382	chr2:179429111;179429110;179429109
Novex-2	18377	55354;55355;55356	chr2:178564384;178564383;178564382	chr2:179429111;179429110;179429109
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-86
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.5543
• Predicted PPI site: I

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
A/T	None	None	1.0	N	0.707	0.313	0.382592752248	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.21507E-04	0
A/V	None	None	1.0	N	0.643	0.435	0.467923293426	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
A/C	0.8739	likely_pathogenic	0.8727	pathogenic	-0.746	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
A/D	0.9421	likely_pathogenic	0.9344	pathogenic	-1.071	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
A/E	0.8803	likely_pathogenic	0.8712	pathogenic	-1.222	Destabilizing	1.0	D	0.727	prob.delet.	N	0.490332195	None	None	I
A/F	0.8416	likely_pathogenic	0.8107	pathogenic	-1.258	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
A/G	0.4379	ambiguous	0.4545	ambiguous	-0.579	Destabilizing	1.0	D	0.541	neutral	N	0.468487813	None	None	I
A/H	0.9399	likely_pathogenic	0.9353	pathogenic	-0.602	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
A/I	0.6948	likely_pathogenic	0.6657	pathogenic	-0.524	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
A/K	0.9621	likely_pathogenic	0.9611	pathogenic	-0.649	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
A/L	0.5604	ambiguous	0.5365	ambiguous	-0.524	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
A/M	0.6362	likely_pathogenic	0.6055	pathogenic	-0.248	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
A/N	0.8407	likely_pathogenic	0.8235	pathogenic	-0.376	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
A/P	0.9681	likely_pathogenic	0.9707	pathogenic	-0.488	Destabilizing	1.0	D	0.722	prob.delet.	N	0.48014465	None	None	I
A/Q	0.8552	likely_pathogenic	0.8543	pathogenic	-0.76	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
A/R	0.9138	likely_pathogenic	0.9104	pathogenic	-0.127	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
A/S	0.2089	likely_benign	0.2154	benign	-0.548	Destabilizing	1.0	D	0.557	neutral	N	0.510880826	None	None	I
A/T	0.3692	ambiguous	0.3488	ambiguous	-0.636	Destabilizing	1.0	D	0.707	prob.neutral	N	0.511707545	None	None	I
A/V	0.461	ambiguous	0.4278	ambiguous	-0.488	Destabilizing	1.0	D	0.643	neutral	N	0.474433431	None	None	I
A/W	0.9818	likely_pathogenic	0.9804	pathogenic	-1.375	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
A/Y	0.9227	likely_pathogenic	0.9134	pathogenic	-1.003	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I

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.