TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17352	52279;52280;52281	chr2:178609256;178609255;178609254	chr2:179473983;179473982;179473981
N2AB	15711	47356;47357;47358	chr2:178609256;178609255;178609254	chr2:179473983;179473982;179473981
N2A	14784	44575;44576;44577	chr2:178609256;178609255;178609254	chr2:179473983;179473982;179473981
N2B	8287	25084;25085;25086	chr2:178609256;178609255;178609254	chr2:179473983;179473982;179473981
Novex-1	8412	25459;25460;25461	chr2:178609256;178609255;178609254	chr2:179473983;179473982;179473981
Novex-2	8479	25660;25661;25662	chr2:178609256;178609255;178609254	chr2:179473983;179473982;179473981
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-112
• Domain position: 102
• Structural Position: 159
• Q(SASA): 0.1845
• 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
E/A	rs1187111699	None	0.999	D	0.677	0.591	0.467416895013	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
E/K	None	None	0.999	N	0.644	0.416	0.407632638399	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	6.17284E-04	0	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
E/A	0.2406	likely_benign	0.2176	benign	-0.775	Destabilizing	0.999	D	0.677	prob.neutral	D	0.527960369	None	None	I
E/C	0.8777	likely_pathogenic	0.8741	pathogenic	-0.238	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
E/D	0.5463	ambiguous	0.4795	ambiguous	-1.015	Destabilizing	0.999	D	0.583	neutral	N	0.487240174	None	None	I
E/F	0.8938	likely_pathogenic	0.8746	pathogenic	-0.698	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
E/G	0.419	ambiguous	0.3647	ambiguous	-1.07	Destabilizing	1.0	D	0.747	deleterious	N	0.506104897	None	None	I
E/H	0.6684	likely_pathogenic	0.638	pathogenic	-0.983	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
E/I	0.4806	ambiguous	0.464	ambiguous	0.005	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
E/K	0.2422	likely_benign	0.2252	benign	-0.285	Destabilizing	0.999	D	0.644	neutral	N	0.494519799	None	None	I
E/L	0.6722	likely_pathogenic	0.6369	pathogenic	0.005	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
E/M	0.573	likely_pathogenic	0.5455	ambiguous	0.48	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
E/N	0.6141	likely_pathogenic	0.5525	ambiguous	-0.62	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
E/P	0.9957	likely_pathogenic	0.9932	pathogenic	-0.234	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
E/Q	0.1433	likely_benign	0.1368	benign	-0.565	Destabilizing	1.0	D	0.737	prob.delet.	D	0.531096674	None	None	I
E/R	0.3875	ambiguous	0.3732	ambiguous	-0.203	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
E/S	0.3223	likely_benign	0.2876	benign	-0.88	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
E/T	0.2836	likely_benign	0.2538	benign	-0.636	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
E/V	0.2774	likely_benign	0.2681	benign	-0.234	Destabilizing	1.0	D	0.803	deleterious	N	0.509894683	None	None	I
E/W	0.9653	likely_pathogenic	0.9583	pathogenic	-0.557	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
E/Y	0.8632	likely_pathogenic	0.8418	pathogenic	-0.454	Destabilizing	1.0	D	0.797	deleterious	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.