TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13942	42049;42050;42051	chr2:178635500;178635499;178635498	chr2:179500227;179500226;179500225
N2AB	12301	37126;37127;37128	chr2:178635500;178635499;178635498	chr2:179500227;179500226;179500225
N2A	11374	34345;34346;34347	chr2:178635500;178635499;178635498	chr2:179500227;179500226;179500225
N2B	4877	14854;14855;14856	chr2:178635500;178635499;178635498	chr2:179500227;179500226;179500225
Novex-1	5002	15229;15230;15231	chr2:178635500;178635499;178635498	chr2:179500227;179500226;179500225
Novex-2	5069	15430;15431;15432	chr2:178635500;178635499;178635498	chr2:179500227;179500226;179500225
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-89
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.2752
• Predicted PPI site: N

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
I/V	rs902514647	-0.902	None	N	0.146	0.038	0.232513804876	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	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
I/A	0.3397	likely_benign	0.2646	benign	-0.903	Destabilizing	0.016	N	0.424	neutral	None	None	None	None	N
I/C	0.8738	likely_pathogenic	0.7912	pathogenic	-0.616	Destabilizing	0.685	D	0.468	neutral	None	None	None	None	N
I/D	0.8714	likely_pathogenic	0.794	pathogenic	-0.285	Destabilizing	0.366	N	0.626	neutral	None	None	None	None	N
I/E	0.7009	likely_pathogenic	0.5895	pathogenic	-0.358	Destabilizing	0.366	N	0.622	neutral	None	None	None	None	N
I/F	0.5238	ambiguous	0.4328	ambiguous	-0.784	Destabilizing	0.177	N	0.454	neutral	N	0.463619975	None	None	N
I/G	0.8302	likely_pathogenic	0.7234	pathogenic	-1.114	Destabilizing	0.366	N	0.609	neutral	None	None	None	None	N
I/H	0.8952	likely_pathogenic	0.82	pathogenic	-0.382	Destabilizing	0.869	D	0.593	neutral	None	None	None	None	N
I/K	0.7498	likely_pathogenic	0.6185	pathogenic	-0.526	Destabilizing	0.366	N	0.603	neutral	None	None	None	None	N
I/L	0.2321	likely_benign	0.183	benign	-0.451	Destabilizing	None	N	0.139	neutral	N	0.461013633	None	None	N
I/M	0.1792	likely_benign	0.1434	benign	-0.383	Destabilizing	0.177	N	0.508	neutral	N	0.466495205	None	None	N
I/N	0.5555	ambiguous	0.4041	ambiguous	-0.295	Destabilizing	0.57	D	0.595	neutral	N	0.444392523	None	None	N
I/P	0.9485	likely_pathogenic	0.9055	pathogenic	-0.568	Destabilizing	0.637	D	0.611	neutral	None	None	None	None	N
I/Q	0.7326	likely_pathogenic	0.6051	pathogenic	-0.514	Destabilizing	0.637	D	0.597	neutral	None	None	None	None	N
I/R	0.7014	likely_pathogenic	0.5821	pathogenic	0.05	Stabilizing	0.366	N	0.599	neutral	None	None	None	None	N
I/S	0.4412	ambiguous	0.3171	benign	-0.801	Destabilizing	0.177	N	0.562	neutral	N	0.433461951	None	None	N
I/T	0.1793	likely_benign	0.1457	benign	-0.762	Destabilizing	0.03	N	0.434	neutral	N	0.45858578	None	None	N
I/V	0.0836	likely_benign	0.0765	benign	-0.568	Destabilizing	None	N	0.146	neutral	N	0.429053499	None	None	N
I/W	0.9689	likely_pathogenic	0.9516	pathogenic	-0.812	Destabilizing	0.869	D	0.632	neutral	None	None	None	None	N
I/Y	0.8701	likely_pathogenic	0.8014	pathogenic	-0.567	Destabilizing	0.366	N	0.517	neutral	None	None	None	None	N

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.