TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21064	63415;63416;63417	chr2:178588217;178588216;178588215	chr2:179452944;179452943;179452942
N2AB	19423	58492;58493;58494	chr2:178588217;178588216;178588215	chr2:179452944;179452943;179452942
N2A	18496	55711;55712;55713	chr2:178588217;178588216;178588215	chr2:179452944;179452943;179452942
N2B	11999	36220;36221;36222	chr2:178588217;178588216;178588215	chr2:179452944;179452943;179452942
Novex-1	12124	36595;36596;36597	chr2:178588217;178588216;178588215	chr2:179452944;179452943;179452942
Novex-2	12191	36796;36797;36798	chr2:178588217;178588216;178588215	chr2:179452944;179452943;179452942
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-41
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4707
• 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
P/A	None	None	0.999	N	0.769	0.341	0.170165803431	gnomAD-4.0.0	1.73766E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.64864E-05	0
P/L	None	None	1.0	N	0.796	0.368	0.499858025796	gnomAD-4.0.0	7.09846E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.23525E-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
P/A	0.1289	likely_benign	0.1369	benign	-0.556	Destabilizing	0.999	D	0.769	deleterious	N	0.508346661	None	None	I
P/C	0.6736	likely_pathogenic	0.6482	pathogenic	-0.658	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
P/D	0.8967	likely_pathogenic	0.8705	pathogenic	-0.131	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
P/E	0.5737	likely_pathogenic	0.5177	ambiguous	-0.245	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
P/F	0.7682	likely_pathogenic	0.7351	pathogenic	-0.781	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
P/G	0.7274	likely_pathogenic	0.7008	pathogenic	-0.689	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
P/H	0.5114	ambiguous	0.4839	ambiguous	-0.218	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
P/I	0.349	ambiguous	0.2987	benign	-0.359	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/K	0.4102	ambiguous	0.3716	ambiguous	-0.3	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/L	0.182	likely_benign	0.1665	benign	-0.359	Destabilizing	1.0	D	0.796	deleterious	N	0.511674968	None	None	I
P/M	0.4138	ambiguous	0.3655	ambiguous	-0.307	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
P/N	0.766	likely_pathogenic	0.7264	pathogenic	-0.068	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
P/Q	0.3278	likely_benign	0.3037	benign	-0.346	Destabilizing	1.0	D	0.811	deleterious	N	0.482506102	None	None	I
P/R	0.3313	likely_benign	0.3058	benign	0.208	Stabilizing	1.0	D	0.818	deleterious	N	0.456804523	None	None	I
P/S	0.398	ambiguous	0.3634	ambiguous	-0.494	Destabilizing	1.0	D	0.818	deleterious	N	0.457564992	None	None	I
P/T	0.2716	likely_benign	0.2428	benign	-0.508	Destabilizing	1.0	D	0.803	deleterious	N	0.458868438	None	None	I
P/V	0.2419	likely_benign	0.2131	benign	-0.39	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
P/W	0.9086	likely_pathogenic	0.897	pathogenic	-0.813	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
P/Y	0.7483	likely_pathogenic	0.7051	pathogenic	-0.501	Destabilizing	1.0	D	0.835	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.