TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29526	88801;88802;88803	chr2:178554883;178554882;178554881	chr2:179419610;179419609;179419608
N2AB	27885	83878;83879;83880	chr2:178554883;178554882;178554881	chr2:179419610;179419609;179419608
N2A	26958	81097;81098;81099	chr2:178554883;178554882;178554881	chr2:179419610;179419609;179419608
N2B	20461	61606;61607;61608	chr2:178554883;178554882;178554881	chr2:179419610;179419609;179419608
Novex-1	20586	61981;61982;61983	chr2:178554883;178554882;178554881	chr2:179419610;179419609;179419608
Novex-2	20653	62182;62183;62184	chr2:178554883;178554882;178554881	chr2:179419610;179419609;179419608
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-146
• Domain position: 83
• Structural Position: 172
• Q(SASA): 0.0625
• 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	rs887166590	-1.085	0.004	N	0.135	0.075	0.460352466543	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
I/V	rs887166590	-1.085	0.004	N	0.135	0.075	0.460352466543	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs887166590	-1.085	0.004	N	0.135	0.075	0.460352466543	gnomAD-4.0.0	3.71792E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08535E-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	0.8545	likely_pathogenic	0.8415	pathogenic	-2.427	Highly Destabilizing	0.702	D	0.659	neutral	None	None	None	None	N
I/C	0.898	likely_pathogenic	0.8809	pathogenic	-1.663	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
I/D	0.9979	likely_pathogenic	0.9975	pathogenic	-2.623	Highly Destabilizing	0.996	D	0.82	deleterious	None	None	None	None	N
I/E	0.9923	likely_pathogenic	0.9909	pathogenic	-2.363	Highly Destabilizing	0.988	D	0.805	deleterious	None	None	None	None	N
I/F	0.3412	ambiguous	0.2957	benign	-1.428	Destabilizing	0.984	D	0.721	prob.delet.	N	0.465103756	None	None	N
I/G	0.9805	likely_pathogenic	0.9772	pathogenic	-3.003	Highly Destabilizing	0.988	D	0.797	deleterious	None	None	None	None	N
I/H	0.9828	likely_pathogenic	0.978	pathogenic	-2.443	Highly Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
I/K	0.9786	likely_pathogenic	0.9737	pathogenic	-1.814	Destabilizing	0.988	D	0.803	deleterious	None	None	None	None	N
I/L	0.2214	likely_benign	0.2101	benign	-0.749	Destabilizing	0.437	N	0.359	neutral	N	0.425966578	None	None	N
I/M	0.2361	likely_benign	0.2179	benign	-0.703	Destabilizing	0.984	D	0.703	prob.neutral	N	0.485189485	None	None	N
I/N	0.9721	likely_pathogenic	0.9672	pathogenic	-2.222	Highly Destabilizing	0.995	D	0.812	deleterious	N	0.520554394	None	None	N
I/P	0.993	likely_pathogenic	0.9907	pathogenic	-1.291	Destabilizing	0.996	D	0.821	deleterious	None	None	None	None	N
I/Q	0.9793	likely_pathogenic	0.9747	pathogenic	-2.018	Highly Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
I/R	0.9649	likely_pathogenic	0.9565	pathogenic	-1.678	Destabilizing	0.988	D	0.816	deleterious	None	None	None	None	N
I/S	0.9451	likely_pathogenic	0.9376	pathogenic	-2.944	Highly Destabilizing	0.984	D	0.771	deleterious	N	0.508817247	None	None	N
I/T	0.9268	likely_pathogenic	0.9175	pathogenic	-2.518	Highly Destabilizing	0.896	D	0.683	prob.neutral	N	0.471299009	None	None	N
I/V	0.0999	likely_benign	0.0969	benign	-1.291	Destabilizing	0.004	N	0.135	neutral	N	0.391392644	None	None	N
I/W	0.9734	likely_pathogenic	0.9653	pathogenic	-1.786	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
I/Y	0.9	likely_pathogenic	0.864	pathogenic	-1.476	Destabilizing	0.996	D	0.791	deleterious	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.