TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35705	107338;107339;107340	chr2:178528638;178528637;178528636	chr2:179393365;179393364;179393363
N2AB	34064	102415;102416;102417	chr2:178528638;178528637;178528636	chr2:179393365;179393364;179393363
N2A	33137	99634;99635;99636	chr2:178528638;178528637;178528636	chr2:179393365;179393364;179393363
N2B	26640	80143;80144;80145	chr2:178528638;178528637;178528636	chr2:179393365;179393364;179393363
Novex-1	26765	80518;80519;80520	chr2:178528638;178528637;178528636	chr2:179393365;179393364;179393363
Novex-2	26832	80719;80720;80721	chr2:178528638;178528637;178528636	chr2:179393365;179393364;179393363
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-168
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5577
• 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/N	None	None	0.963	N	0.383	0.399	0.757895655473	gnomAD-4.0.0	1.59346E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02663E-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
I/A	0.5846	likely_pathogenic	0.6959	pathogenic	-0.819	Destabilizing	0.25	N	0.347	neutral	None	None	None	None	N
I/C	0.8546	likely_pathogenic	0.9044	pathogenic	-0.684	Destabilizing	0.992	D	0.333	neutral	None	None	None	None	N
I/D	0.8735	likely_pathogenic	0.9594	pathogenic	-0.056	Destabilizing	0.972	D	0.406	neutral	None	None	None	None	N
I/E	0.7852	likely_pathogenic	0.9209	pathogenic	-0.128	Destabilizing	0.92	D	0.399	neutral	None	None	None	None	N
I/F	0.2267	likely_benign	0.327	benign	-0.675	Destabilizing	0.681	D	0.306	neutral	N	0.458947798	None	None	N
I/G	0.864	likely_pathogenic	0.9297	pathogenic	-1.02	Destabilizing	0.92	D	0.386	neutral	None	None	None	None	N
I/H	0.6178	likely_pathogenic	0.8506	pathogenic	-0.202	Destabilizing	0.992	D	0.364	neutral	None	None	None	None	N
I/K	0.5497	ambiguous	0.7948	pathogenic	-0.394	Destabilizing	0.92	D	0.393	neutral	None	None	None	None	N
I/L	0.14	likely_benign	0.1592	benign	-0.401	Destabilizing	0.001	N	0.097	neutral	N	0.398333606	None	None	N
I/M	0.1949	likely_benign	0.2525	benign	-0.382	Destabilizing	0.81	D	0.372	neutral	N	0.463867952	None	None	N
I/N	0.4531	ambiguous	0.7296	pathogenic	-0.218	Destabilizing	0.963	D	0.383	neutral	N	0.503098344	None	None	N
I/P	0.9081	likely_pathogenic	0.9333	pathogenic	-0.506	Destabilizing	0.972	D	0.401	neutral	None	None	None	None	N
I/Q	0.5995	likely_pathogenic	0.8195	pathogenic	-0.436	Destabilizing	0.972	D	0.369	neutral	None	None	None	None	N
I/R	0.4192	ambiguous	0.7065	pathogenic	0.174	Stabilizing	0.92	D	0.394	neutral	None	None	None	None	N
I/S	0.4652	ambiguous	0.6623	pathogenic	-0.768	Destabilizing	0.549	D	0.378	neutral	N	0.457056623	None	None	N
I/T	0.3665	ambiguous	0.5818	pathogenic	-0.727	Destabilizing	0.549	D	0.332	neutral	N	0.397776246	None	None	N
I/V	0.1153	likely_benign	0.1324	benign	-0.506	Destabilizing	0.002	N	0.113	neutral	N	0.438006715	None	None	N
I/W	0.8704	likely_pathogenic	0.9378	pathogenic	-0.67	Destabilizing	0.992	D	0.425	neutral	None	None	None	None	N
I/Y	0.6371	likely_pathogenic	0.7845	pathogenic	-0.425	Destabilizing	0.92	D	0.366	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.