TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29853	89782;89783;89784	chr2:178553343;178553342;178553341	chr2:179418070;179418069;179418068
N2AB	28212	84859;84860;84861	chr2:178553343;178553342;178553341	chr2:179418070;179418069;179418068
N2A	27285	82078;82079;82080	chr2:178553343;178553342;178553341	chr2:179418070;179418069;179418068
N2B	20788	62587;62588;62589	chr2:178553343;178553342;178553341	chr2:179418070;179418069;179418068
Novex-1	20913	62962;62963;62964	chr2:178553343;178553342;178553341	chr2:179418070;179418069;179418068
Novex-2	20980	63163;63164;63165	chr2:178553343;178553342;178553341	chr2:179418070;179418069;179418068
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: Ig-147
• Domain position: 12
• Structural Position: 23
• Q(SASA): 0.5733
• 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	rs1337052263	None	1.0	N	0.721	0.326	0.253726318573	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs1337052263	None	1.0	N	0.721	0.326	0.253726318573	gnomAD-4.0.0	6.57142E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46994E-05	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	0.712	likely_pathogenic	0.6924	pathogenic	-0.805	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
A/D	0.7918	likely_pathogenic	0.7618	pathogenic	-0.879	Destabilizing	1.0	D	0.8	deleterious	N	0.480837488	None	None	I
A/E	0.6827	likely_pathogenic	0.6619	pathogenic	-1.026	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
A/F	0.7686	likely_pathogenic	0.7364	pathogenic	-1.102	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
A/G	0.3597	ambiguous	0.3262	benign	-0.67	Destabilizing	1.0	D	0.56	neutral	N	0.507589024	None	None	I
A/H	0.7915	likely_pathogenic	0.7881	pathogenic	-0.695	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
A/I	0.6452	likely_pathogenic	0.5751	pathogenic	-0.531	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
A/K	0.8077	likely_pathogenic	0.8178	pathogenic	-0.954	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
A/L	0.6044	likely_pathogenic	0.56	ambiguous	-0.531	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
A/M	0.5904	likely_pathogenic	0.5271	ambiguous	-0.418	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
A/N	0.6566	likely_pathogenic	0.6129	pathogenic	-0.578	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
A/P	0.9036	likely_pathogenic	0.8546	pathogenic	-0.512	Destabilizing	1.0	D	0.761	deleterious	N	0.461719275	None	None	I
A/Q	0.6427	likely_pathogenic	0.6513	pathogenic	-0.901	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
A/R	0.7147	likely_pathogenic	0.7315	pathogenic	-0.401	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
A/S	0.1616	likely_benign	0.1526	benign	-0.777	Destabilizing	1.0	D	0.571	neutral	N	0.506445293	None	None	I
A/T	0.333	likely_benign	0.2937	benign	-0.852	Destabilizing	1.0	D	0.721	prob.delet.	N	0.468467225	None	None	I
A/V	0.3158	likely_benign	0.2566	benign	-0.512	Destabilizing	1.0	D	0.653	neutral	N	0.496110869	None	None	I
A/W	0.9494	likely_pathogenic	0.9372	pathogenic	-1.24	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
A/Y	0.8138	likely_pathogenic	0.7927	pathogenic	-0.913	Destabilizing	1.0	D	0.794	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.