TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9222	27889;27890;27891	chr2:178712166;178712165;178712164	chr2:179576893;179576892;179576891
N2AB	8905	26938;26939;26940	chr2:178712166;178712165;178712164	chr2:179576893;179576892;179576891
N2A	7978	24157;24158;24159	chr2:178712166;178712165;178712164	chr2:179576893;179576892;179576891
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-78
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2613
• Predicted PPI site: I

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
A/S	None	None	0.959	N	0.615	0.279	0.163833314356	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
A/V	rs786205313	-0.019	0.061	N	0.238	0.221	0.15556083564	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
A/V	rs786205313	-0.019	0.061	N	0.238	0.221	0.15556083564	gnomAD-4.0.0	7.95639E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88239E-05	0	1.14336E-05	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
A/C	0.6051	likely_pathogenic	0.5966	pathogenic	-0.927	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	I
A/D	0.9323	likely_pathogenic	0.9486	pathogenic	0.143	Stabilizing	0.996	D	0.701	prob.neutral	N	0.500982886	None	None	I
A/E	0.8995	likely_pathogenic	0.9103	pathogenic	0.2	Stabilizing	0.997	D	0.713	prob.delet.	None	None	None	None	I
A/F	0.6001	likely_pathogenic	0.6816	pathogenic	-0.456	Destabilizing	0.046	N	0.441	neutral	None	None	None	None	I
A/G	0.2982	likely_benign	0.3265	benign	-0.881	Destabilizing	0.986	D	0.599	neutral	N	0.466242407	None	None	I
A/H	0.9314	likely_pathogenic	0.9365	pathogenic	-0.867	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	I
A/I	0.2652	likely_benign	0.3059	benign	0.223	Stabilizing	0.884	D	0.583	neutral	None	None	None	None	I
A/K	0.9376	likely_pathogenic	0.9399	pathogenic	-0.566	Destabilizing	0.997	D	0.715	prob.delet.	None	None	None	None	I
A/L	0.3216	likely_benign	0.3473	ambiguous	0.223	Stabilizing	0.759	D	0.544	neutral	None	None	None	None	I
A/M	0.3922	ambiguous	0.4383	ambiguous	-0.179	Destabilizing	0.991	D	0.709	prob.delet.	None	None	None	None	I
A/N	0.8572	likely_pathogenic	0.8799	pathogenic	-0.52	Destabilizing	0.997	D	0.716	prob.delet.	None	None	None	None	I
A/P	0.9257	likely_pathogenic	0.9462	pathogenic	0.008	Stabilizing	0.996	D	0.717	prob.delet.	N	0.489208507	None	None	I
A/Q	0.8824	likely_pathogenic	0.8826	pathogenic	-0.426	Destabilizing	0.997	D	0.713	prob.delet.	None	None	None	None	I
A/R	0.8976	likely_pathogenic	0.9013	pathogenic	-0.583	Destabilizing	0.997	D	0.718	prob.delet.	None	None	None	None	I
A/S	0.2142	likely_benign	0.2282	benign	-1.1	Destabilizing	0.959	D	0.615	neutral	N	0.470850762	None	None	I
A/T	0.1081	likely_benign	0.1058	benign	-0.887	Destabilizing	0.92	D	0.598	neutral	N	0.470833997	None	None	I
A/V	0.1206	likely_benign	0.1324	benign	0.008	Stabilizing	0.061	N	0.238	neutral	N	0.381881287	None	None	I
A/W	0.9652	likely_pathogenic	0.9738	pathogenic	-0.798	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
A/Y	0.8653	likely_pathogenic	0.89	pathogenic	-0.321	Destabilizing	0.964	D	0.699	prob.neutral	None	None	None	None	I

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.