TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21644	65155;65156;65157	chr2:178584711;178584710;178584709	chr2:179449438;179449437;179449436
N2AB	20003	60232;60233;60234	chr2:178584711;178584710;178584709	chr2:179449438;179449437;179449436
N2A	19076	57451;57452;57453	chr2:178584711;178584710;178584709	chr2:179449438;179449437;179449436
N2B	12579	37960;37961;37962	chr2:178584711;178584710;178584709	chr2:179449438;179449437;179449436
Novex-1	12704	38335;38336;38337	chr2:178584711;178584710;178584709	chr2:179449438;179449437;179449436
Novex-2	12771	38536;38537;38538	chr2:178584711;178584710;178584709	chr2:179449438;179449437;179449436
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-44
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.5425
• 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
E/K	None	None	0.961	N	0.602	0.265	0.294206760003	gnomAD-4.0.0	2.053E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69884E-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
E/A	0.1479	likely_benign	0.1633	benign	-0.674	Destabilizing	0.98	D	0.597	neutral	N	0.52165518	None	None	I
E/C	0.816	likely_pathogenic	0.821	pathogenic	-0.206	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
E/D	0.0936	likely_benign	0.0956	benign	-0.636	Destabilizing	0.135	N	0.276	neutral	N	0.422416479	None	None	I
E/F	0.7704	likely_pathogenic	0.7609	pathogenic	-0.473	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
E/G	0.1852	likely_benign	0.1985	benign	-0.908	Destabilizing	0.99	D	0.63	neutral	N	0.487484803	None	None	I
E/H	0.4519	ambiguous	0.4602	ambiguous	-0.38	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	I
E/I	0.3718	ambiguous	0.3728	ambiguous	-0.076	Destabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	I
E/K	0.1394	likely_benign	0.1507	benign	0.012	Stabilizing	0.961	D	0.602	neutral	N	0.514825208	None	None	I
E/L	0.3554	ambiguous	0.3523	ambiguous	-0.076	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	I
E/M	0.4647	ambiguous	0.4708	ambiguous	0.155	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
E/N	0.2265	likely_benign	0.2379	benign	-0.351	Destabilizing	0.985	D	0.585	neutral	None	None	None	None	I
E/P	0.3077	likely_benign	0.3546	ambiguous	-0.256	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	I
E/Q	0.1307	likely_benign	0.1365	benign	-0.315	Destabilizing	0.817	D	0.301	neutral	N	0.504320213	None	None	I
E/R	0.2673	likely_benign	0.2793	benign	0.251	Stabilizing	0.996	D	0.566	neutral	None	None	None	None	I
E/S	0.1824	likely_benign	0.191	benign	-0.527	Destabilizing	0.971	D	0.563	neutral	None	None	None	None	I
E/T	0.2327	likely_benign	0.2375	benign	-0.338	Destabilizing	0.671	D	0.361	neutral	None	None	None	None	I
E/V	0.2174	likely_benign	0.2257	benign	-0.256	Destabilizing	0.994	D	0.587	neutral	N	0.473383474	None	None	I
E/W	0.906	likely_pathogenic	0.9042	pathogenic	-0.263	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
E/Y	0.5853	likely_pathogenic	0.5846	pathogenic	-0.223	Destabilizing	0.999	D	0.698	prob.neutral	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.