TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15483	46672;46673;46674	chr2:178619870;178619869;178619868	chr2:179484597;179484596;179484595
N2AB	13842	41749;41750;41751	chr2:178619870;178619869;178619868	chr2:179484597;179484596;179484595
N2A	12915	38968;38969;38970	chr2:178619870;178619869;178619868	chr2:179484597;179484596;179484595
N2B	6418	19477;19478;19479	chr2:178619870;178619869;178619868	chr2:179484597;179484596;179484595
Novex-1	6543	19852;19853;19854	chr2:178619870;178619869;178619868	chr2:179484597;179484596;179484595
Novex-2	6610	20053;20054;20055	chr2:178619870;178619869;178619868	chr2:179484597;179484596;179484595
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-107
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3467
• 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	None	None	0.198	N	0.202	0.256	0.634606890218	gnomAD-4.0.0	1.59994E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86775E-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
I/A	0.6876	likely_pathogenic	0.7281	pathogenic	-1.306	Destabilizing	0.983	D	0.417	neutral	None	None	None	None	N
I/C	0.8541	likely_pathogenic	0.8915	pathogenic	-0.671	Destabilizing	1.0	D	0.553	neutral	None	None	None	None	N
I/D	0.9277	likely_pathogenic	0.9515	pathogenic	-0.935	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
I/E	0.7999	likely_pathogenic	0.8459	pathogenic	-0.988	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
I/F	0.378	ambiguous	0.4166	ambiguous	-1.013	Destabilizing	0.997	D	0.486	neutral	D	0.539230294	None	None	N
I/G	0.8848	likely_pathogenic	0.9152	pathogenic	-1.556	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
I/H	0.7497	likely_pathogenic	0.812	pathogenic	-0.771	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
I/K	0.5686	likely_pathogenic	0.6462	pathogenic	-0.932	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
I/L	0.179	likely_benign	0.1771	benign	-0.724	Destabilizing	0.798	D	0.333	neutral	N	0.454142723	None	None	N
I/M	0.2203	likely_benign	0.2336	benign	-0.509	Destabilizing	0.997	D	0.485	neutral	D	0.529182271	None	None	N
I/N	0.5764	likely_pathogenic	0.6633	pathogenic	-0.66	Destabilizing	0.999	D	0.675	prob.neutral	D	0.547474159	None	None	N
I/P	0.9604	likely_pathogenic	0.9601	pathogenic	-0.886	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
I/Q	0.6453	likely_pathogenic	0.7074	pathogenic	-0.909	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
I/R	0.5097	ambiguous	0.5943	pathogenic	-0.247	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
I/S	0.589	likely_pathogenic	0.6597	pathogenic	-1.143	Destabilizing	0.997	D	0.581	neutral	D	0.529398576	None	None	N
I/T	0.3864	ambiguous	0.4111	ambiguous	-1.095	Destabilizing	0.978	D	0.468	neutral	N	0.516379705	None	None	N
I/V	0.1104	likely_benign	0.1092	benign	-0.886	Destabilizing	0.198	N	0.202	neutral	N	0.466756283	None	None	N
I/W	0.9121	likely_pathogenic	0.9346	pathogenic	-1.051	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
I/Y	0.7612	likely_pathogenic	0.8198	pathogenic	-0.85	Destabilizing	0.999	D	0.545	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.