TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4727	14404;14405;14406	chr2:178738274;178738273;178738272	chr2:179603001;179603000;179602999
N2AB	4410	13453;13454;13455	chr2:178738274;178738273;178738272	chr2:179603001;179603000;179602999
N2A	3483	10672;10673;10674	chr2:178738274;178738273;178738272	chr2:179603001;179603000;179602999
N2B	4364	13315;13316;13317	chr2:178738274;178738273;178738272	chr2:179603001;179603000;179602999
Novex-1	4489	13690;13691;13692	chr2:178738274;178738273;178738272	chr2:179603001;179603000;179602999
Novex-2	4556	13891;13892;13893	chr2:178738274;178738273;178738272	chr2:179603001;179603000;179602999
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-30
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.4712
• 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/S	rs1212488962	-0.207	1.0	N	0.747	0.693	0.488477830397	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
P/S	rs1212488962	-0.207	1.0	N	0.747	0.693	0.488477830397	gnomAD-4.0.0	2.60045E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.05841E-05	0	6.6291E-05

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	0.2032	likely_benign	0.414	ambiguous	-1.201	Destabilizing	1.0	D	0.71	prob.delet.	N	0.499490525	None	None	I
P/C	0.8379	likely_pathogenic	0.9479	pathogenic	-0.6	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
P/D	0.6536	likely_pathogenic	0.8735	pathogenic	-1.137	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/E	0.4551	ambiguous	0.7266	pathogenic	-1.161	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
P/F	0.8532	likely_pathogenic	0.9639	pathogenic	-1.019	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
P/G	0.5856	likely_pathogenic	0.8061	pathogenic	-1.47	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
P/H	0.4459	ambiguous	0.7304	pathogenic	-1.034	Destabilizing	1.0	D	0.686	prob.neutral	N	0.505501582	None	None	I
P/I	0.7207	likely_pathogenic	0.8948	pathogenic	-0.574	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
P/K	0.5083	ambiguous	0.7573	pathogenic	-1.003	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/L	0.3435	ambiguous	0.6112	pathogenic	-0.574	Destabilizing	1.0	D	0.7	prob.neutral	N	0.505501582	None	None	I
P/M	0.715	likely_pathogenic	0.8959	pathogenic	-0.426	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
P/N	0.6404	likely_pathogenic	0.8639	pathogenic	-0.7	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
P/Q	0.3404	ambiguous	0.6381	pathogenic	-0.89	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
P/R	0.336	likely_benign	0.6176	pathogenic	-0.474	Destabilizing	1.0	D	0.719	prob.delet.	N	0.499806253	None	None	I
P/S	0.2791	likely_benign	0.5563	ambiguous	-1.104	Destabilizing	1.0	D	0.747	deleterious	N	0.498921175	None	None	I
P/T	0.2903	likely_benign	0.5363	ambiguous	-1.025	Destabilizing	1.0	D	0.741	deleterious	N	0.499806253	None	None	I
P/V	0.5611	ambiguous	0.7826	pathogenic	-0.749	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
P/W	0.8882	likely_pathogenic	0.9716	pathogenic	-1.199	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
P/Y	0.8045	likely_pathogenic	0.9435	pathogenic	-0.907	Destabilizing	1.0	D	0.734	prob.delet.	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.