TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25352	76279;76280;76281	chr2:178570078;178570077;178570076	chr2:179434805;179434804;179434803
N2AB	23711	71356;71357;71358	chr2:178570078;178570077;178570076	chr2:179434805;179434804;179434803
N2A	22784	68575;68576;68577	chr2:178570078;178570077;178570076	chr2:179434805;179434804;179434803
N2B	16287	49084;49085;49086	chr2:178570078;178570077;178570076	chr2:179434805;179434804;179434803
Novex-1	16412	49459;49460;49461	chr2:178570078;178570077;178570076	chr2:179434805;179434804;179434803
Novex-2	16479	49660;49661;49662	chr2:178570078;178570077;178570076	chr2:179434805;179434804;179434803
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-72
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.376
• 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
T/R	rs1318162597	-0.236	0.89	N	0.555	0.319	0.500931478032	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/R	rs1318162597	-0.236	0.89	N	0.555	0.319	0.500931478032	gnomAD-4.0.0	4.7762E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41779E-04	0	2.86582E-05	0
T/S	None	None	0.058	N	0.288	0.133	0.107399877778	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

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
T/A	0.1222	likely_benign	0.1346	benign	-0.642	Destabilizing	0.489	N	0.513	neutral	N	0.464834645	None	None	I
T/C	0.4503	ambiguous	0.5034	ambiguous	-0.38	Destabilizing	0.998	D	0.582	neutral	None	None	None	None	I
T/D	0.8559	likely_pathogenic	0.8522	pathogenic	0.158	Stabilizing	0.956	D	0.531	neutral	None	None	None	None	I
T/E	0.7395	likely_pathogenic	0.7288	pathogenic	0.142	Stabilizing	0.754	D	0.491	neutral	None	None	None	None	I
T/F	0.3558	ambiguous	0.3711	ambiguous	-0.757	Destabilizing	0.978	D	0.627	neutral	None	None	None	None	I
T/G	0.3337	likely_benign	0.3691	ambiguous	-0.874	Destabilizing	0.754	D	0.515	neutral	None	None	None	None	I
T/H	0.4585	ambiguous	0.4641	ambiguous	-1.043	Destabilizing	0.994	D	0.627	neutral	None	None	None	None	I
T/I	0.1438	likely_benign	0.1517	benign	-0.126	Destabilizing	0.971	D	0.591	neutral	N	0.467706052	None	None	I
T/K	0.5838	likely_pathogenic	0.5577	ambiguous	-0.594	Destabilizing	0.032	N	0.276	neutral	N	0.504125425	None	None	I
T/L	0.1206	likely_benign	0.1337	benign	-0.126	Destabilizing	0.86	D	0.492	neutral	None	None	None	None	I
T/M	0.0936	likely_benign	0.0997	benign	-0.003	Destabilizing	0.998	D	0.577	neutral	None	None	None	None	I
T/N	0.2024	likely_benign	0.2153	benign	-0.443	Destabilizing	0.915	D	0.511	neutral	None	None	None	None	I
T/P	0.6803	likely_pathogenic	0.6677	pathogenic	-0.266	Destabilizing	0.971	D	0.585	neutral	N	0.505286343	None	None	I
T/Q	0.3914	ambiguous	0.3921	ambiguous	-0.583	Destabilizing	0.956	D	0.589	neutral	None	None	None	None	I
T/R	0.5426	ambiguous	0.5071	ambiguous	-0.336	Destabilizing	0.89	D	0.555	neutral	N	0.505338933	None	None	I
T/S	0.1603	likely_benign	0.1712	benign	-0.74	Destabilizing	0.058	N	0.288	neutral	N	0.509187315	None	None	I
T/V	0.1176	likely_benign	0.1272	benign	-0.266	Destabilizing	0.86	D	0.487	neutral	None	None	None	None	I
T/W	0.7771	likely_pathogenic	0.7771	pathogenic	-0.718	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	I
T/Y	0.4516	ambiguous	0.4654	ambiguous	-0.484	Destabilizing	0.993	D	0.629	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.