TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14609	44050;44051;44052	chr2:178631223;178631222;178631221	chr2:179495950;179495949;179495948
N2AB	12968	39127;39128;39129	chr2:178631223;178631222;178631221	chr2:179495950;179495949;179495948
N2A	12041	36346;36347;36348	chr2:178631223;178631222;178631221	chr2:179495950;179495949;179495948
N2B	5544	16855;16856;16857	chr2:178631223;178631222;178631221	chr2:179495950;179495949;179495948
Novex-1	5669	17230;17231;17232	chr2:178631223;178631222;178631221	chr2:179495950;179495949;179495948
Novex-2	5736	17431;17432;17433	chr2:178631223;178631222;178631221	chr2:179495950;179495949;179495948
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-97
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0925
• 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/L	None	None	0.005	N	0.269	0.176	0.247322355667	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9092	likely_pathogenic	0.9054	pathogenic	-3.11	Highly Destabilizing	0.863	D	0.639	neutral	None	None	None	None	N
I/C	0.9753	likely_pathogenic	0.978	pathogenic	-2.475	Highly Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
I/D	0.9925	likely_pathogenic	0.9947	pathogenic	-3.473	Highly Destabilizing	0.997	D	0.809	deleterious	None	None	None	None	N
I/E	0.9851	likely_pathogenic	0.9884	pathogenic	-3.237	Highly Destabilizing	0.997	D	0.805	deleterious	None	None	None	None	N
I/F	0.7276	likely_pathogenic	0.7922	pathogenic	-1.735	Destabilizing	0.976	D	0.701	prob.neutral	N	0.518181263	None	None	N
I/G	0.9809	likely_pathogenic	0.9833	pathogenic	-3.591	Highly Destabilizing	0.997	D	0.793	deleterious	None	None	None	None	N
I/H	0.9895	likely_pathogenic	0.9928	pathogenic	-2.801	Highly Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
I/K	0.9715	likely_pathogenic	0.978	pathogenic	-2.213	Highly Destabilizing	0.997	D	0.797	deleterious	None	None	None	None	N
I/L	0.3173	likely_benign	0.2848	benign	-1.677	Destabilizing	0.005	N	0.269	neutral	N	0.390846717	None	None	N
I/M	0.3303	likely_benign	0.3275	benign	-1.917	Destabilizing	0.976	D	0.667	neutral	D	0.588765359	None	None	N
I/N	0.9005	likely_pathogenic	0.9218	pathogenic	-2.653	Highly Destabilizing	0.996	D	0.814	deleterious	D	0.631399776	None	None	N
I/P	0.9905	likely_pathogenic	0.9918	pathogenic	-2.145	Highly Destabilizing	0.997	D	0.813	deleterious	None	None	None	None	N
I/Q	0.9837	likely_pathogenic	0.9875	pathogenic	-2.49	Highly Destabilizing	0.997	D	0.812	deleterious	None	None	None	None	N
I/R	0.9656	likely_pathogenic	0.9745	pathogenic	-1.932	Destabilizing	0.997	D	0.816	deleterious	None	None	None	None	N
I/S	0.9181	likely_pathogenic	0.9299	pathogenic	-3.255	Highly Destabilizing	0.988	D	0.759	deleterious	N	0.518016493	None	None	N
I/T	0.8267	likely_pathogenic	0.7981	pathogenic	-2.892	Highly Destabilizing	0.92	D	0.685	prob.neutral	N	0.505917299	None	None	N
I/V	0.1737	likely_benign	0.1498	benign	-2.145	Highly Destabilizing	0.061	N	0.259	neutral	N	0.375535235	None	None	N
I/W	0.9922	likely_pathogenic	0.9956	pathogenic	-1.985	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
I/Y	0.959	likely_pathogenic	0.9756	pathogenic	-1.912	Destabilizing	0.997	D	0.764	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.