TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31889	95890;95891;95892	chr2:178545445;178545444;178545443	chr2:179410172;179410171;179410170
N2AB	30248	90967;90968;90969	chr2:178545445;178545444;178545443	chr2:179410172;179410171;179410170
N2A	29321	88186;88187;88188	chr2:178545445;178545444;178545443	chr2:179410172;179410171;179410170
N2B	22824	68695;68696;68697	chr2:178545445;178545444;178545443	chr2:179410172;179410171;179410170
Novex-1	22949	69070;69071;69072	chr2:178545445;178545444;178545443	chr2:179410172;179410171;179410170
Novex-2	23016	69271;69272;69273	chr2:178545445;178545444;178545443	chr2:179410172;179410171;179410170
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-120
• Domain position: 83
• Structural Position: 114
• Q(SASA): 0.6051
• 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	rs1025105445	None	1.0	N	0.768	0.46	0.384252928164	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs1025105445	None	1.0	N	0.768	0.46	0.384252928164	gnomAD-4.0.0	3.04476E-06	None	None	None	None	I	None	1.74709E-05	6.14931E-05	None	0	0	None	0	0	1.20492E-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	0.7672	likely_pathogenic	0.7452	pathogenic	-0.881	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
A/D	0.9712	likely_pathogenic	0.9735	pathogenic	-0.758	Destabilizing	1.0	D	0.857	deleterious	N	0.518706564	None	None	I
A/E	0.9102	likely_pathogenic	0.918	pathogenic	-0.916	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
A/F	0.7857	likely_pathogenic	0.7504	pathogenic	-0.959	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
A/G	0.4875	ambiguous	0.4986	ambiguous	-0.329	Destabilizing	1.0	D	0.619	neutral	N	0.503614049	None	None	I
A/H	0.9502	likely_pathogenic	0.9467	pathogenic	-0.258	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
A/I	0.6615	likely_pathogenic	0.7104	pathogenic	-0.456	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
A/K	0.9798	likely_pathogenic	0.984	pathogenic	-0.709	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
A/L	0.7095	likely_pathogenic	0.7274	pathogenic	-0.456	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
A/M	0.691	likely_pathogenic	0.6991	pathogenic	-0.562	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
A/N	0.912	likely_pathogenic	0.9238	pathogenic	-0.421	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
A/P	0.9771	likely_pathogenic	0.9811	pathogenic	-0.379	Destabilizing	1.0	D	0.8	deleterious	D	0.538585245	None	None	I
A/Q	0.9088	likely_pathogenic	0.9122	pathogenic	-0.726	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
A/R	0.9433	likely_pathogenic	0.9501	pathogenic	-0.174	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
A/S	0.2617	likely_benign	0.2766	benign	-0.576	Destabilizing	1.0	D	0.624	neutral	N	0.474535563	None	None	I
A/T	0.5727	likely_pathogenic	0.605	pathogenic	-0.664	Destabilizing	1.0	D	0.768	deleterious	N	0.508110727	None	None	I
A/V	0.3948	ambiguous	0.4325	ambiguous	-0.379	Destabilizing	1.0	D	0.715	prob.delet.	N	0.492121707	None	None	I
A/W	0.9777	likely_pathogenic	0.9773	pathogenic	-1.056	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
A/Y	0.9201	likely_pathogenic	0.908	pathogenic	-0.742	Destabilizing	1.0	D	0.858	deleterious	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.