TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21239	63940;63941;63942	chr2:178587594;178587593;178587592	chr2:179452321;179452320;179452319
N2AB	19598	59017;59018;59019	chr2:178587594;178587593;178587592	chr2:179452321;179452320;179452319
N2A	18671	56236;56237;56238	chr2:178587594;178587593;178587592	chr2:179452321;179452320;179452319
N2B	12174	36745;36746;36747	chr2:178587594;178587593;178587592	chr2:179452321;179452320;179452319
Novex-1	12299	37120;37121;37122	chr2:178587594;178587593;178587592	chr2:179452321;179452320;179452319
Novex-2	12366	37321;37322;37323	chr2:178587594;178587593;178587592	chr2:179452321;179452320;179452319
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-123
• Domain position: 63
• Structural Position: 148
• Q(SASA): 0.8634
• 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
D/E	None	None	0.619	N	0.268	0.069	0.204665344411	gnomAD-4.0.0	1.59406E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86148E-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
D/A	0.1664	likely_benign	0.1791	benign	-0.143	Destabilizing	0.992	D	0.651	neutral	N	0.471831287	None	None	I
D/C	0.639	likely_pathogenic	0.6696	pathogenic	0.187	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
D/E	0.1108	likely_benign	0.1265	benign	-0.167	Destabilizing	0.619	D	0.268	neutral	N	0.409894607	None	None	I
D/F	0.5722	likely_pathogenic	0.6211	pathogenic	-0.273	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
D/G	0.2087	likely_benign	0.2308	benign	-0.288	Destabilizing	0.996	D	0.703	prob.neutral	N	0.483221717	None	None	I
D/H	0.3341	likely_benign	0.3402	ambiguous	-0.013	Destabilizing	1.0	D	0.728	prob.delet.	N	0.508773522	None	None	I
D/I	0.3933	ambiguous	0.4301	ambiguous	0.175	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
D/K	0.4565	ambiguous	0.4576	ambiguous	0.468	Stabilizing	0.998	D	0.72	prob.delet.	None	None	None	None	I
D/L	0.3645	ambiguous	0.3905	ambiguous	0.175	Stabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
D/M	0.545	ambiguous	0.604	pathogenic	0.294	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
D/N	0.1116	likely_benign	0.1251	benign	0.311	Stabilizing	0.999	D	0.721	prob.delet.	N	0.457555268	None	None	I
D/P	0.8619	likely_pathogenic	0.8837	pathogenic	0.09	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/Q	0.3227	likely_benign	0.3354	benign	0.312	Stabilizing	0.998	D	0.754	deleterious	None	None	None	None	I
D/R	0.4992	ambiguous	0.5053	ambiguous	0.565	Stabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	I
D/S	0.1433	likely_benign	0.1581	benign	0.192	Stabilizing	0.994	D	0.677	prob.neutral	None	None	None	None	I
D/T	0.2418	likely_benign	0.2755	benign	0.301	Stabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	I
D/V	0.2375	likely_benign	0.2556	benign	0.09	Stabilizing	0.999	D	0.748	deleterious	N	0.512717905	None	None	I
D/W	0.8652	likely_pathogenic	0.883	pathogenic	-0.216	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
D/Y	0.2302	likely_benign	0.2399	benign	-0.05	Destabilizing	1.0	D	0.755	deleterious	N	0.452650881	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.