TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24114	72565;72566;72567	chr2:178573792;178573791;178573790	chr2:179438519;179438518;179438517
N2AB	22473	67642;67643;67644	chr2:178573792;178573791;178573790	chr2:179438519;179438518;179438517
N2A	21546	64861;64862;64863	chr2:178573792;178573791;178573790	chr2:179438519;179438518;179438517
N2B	15049	45370;45371;45372	chr2:178573792;178573791;178573790	chr2:179438519;179438518;179438517
Novex-1	15174	45745;45746;45747	chr2:178573792;178573791;178573790	chr2:179438519;179438518;179438517
Novex-2	15241	45946;45947;45948	chr2:178573792;178573791;178573790	chr2:179438519;179438518;179438517
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-131
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.413
• 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/N	None	None	0.927	N	0.669	0.279	0.736317021544	gnomAD-4.0.0	2.74366E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60412E-06	0	0
I/V	None	None	0.001	N	0.179	0.103	0.5073929853	gnomAD-4.0.0	1.60077E-06	None	None	None	None	N	None	0	2.31E-05	None	0	0	None	0	0	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
I/A	0.1971	likely_benign	0.2319	benign	-1.22	Destabilizing	0.176	N	0.39	neutral	None	None	None	None	N
I/C	0.4437	ambiguous	0.522	ambiguous	-0.526	Destabilizing	0.981	D	0.609	neutral	None	None	None	None	N
I/D	0.4207	ambiguous	0.4865	ambiguous	-0.619	Destabilizing	0.828	D	0.672	neutral	None	None	None	None	N
I/E	0.3744	ambiguous	0.4138	ambiguous	-0.665	Destabilizing	0.828	D	0.654	neutral	None	None	None	None	N
I/F	0.1343	likely_benign	0.1608	benign	-1.001	Destabilizing	0.784	D	0.58	neutral	N	0.441341462	None	None	N
I/G	0.4202	ambiguous	0.4891	ambiguous	-1.481	Destabilizing	0.828	D	0.62	neutral	None	None	None	None	N
I/H	0.2573	likely_benign	0.3068	benign	-0.724	Destabilizing	0.995	D	0.621	neutral	None	None	None	None	N
I/K	0.2389	likely_benign	0.2896	benign	-0.652	Destabilizing	0.828	D	0.657	neutral	None	None	None	None	N
I/L	0.1027	likely_benign	0.1125	benign	-0.607	Destabilizing	0.139	N	0.314	neutral	N	0.446112563	None	None	N
I/M	0.1041	likely_benign	0.118	benign	-0.397	Destabilizing	0.927	D	0.603	neutral	N	0.487940543	None	None	N
I/N	0.1343	likely_benign	0.1588	benign	-0.332	Destabilizing	0.927	D	0.669	neutral	N	0.417944527	None	None	N
I/P	0.6073	likely_pathogenic	0.6599	pathogenic	-0.778	Destabilizing	0.981	D	0.669	neutral	None	None	None	None	N
I/Q	0.2761	likely_benign	0.3113	benign	-0.552	Destabilizing	0.981	D	0.657	neutral	None	None	None	None	N
I/R	0.1831	likely_benign	0.222	benign	-0.06	Destabilizing	0.944	D	0.669	neutral	None	None	None	None	N
I/S	0.1382	likely_benign	0.1618	benign	-0.865	Destabilizing	0.27	N	0.543	neutral	N	0.35623992	None	None	N
I/T	0.1046	likely_benign	0.121	benign	-0.796	Destabilizing	0.003	N	0.292	neutral	N	0.346081642	None	None	N
I/V	0.0588	likely_benign	0.063	benign	-0.778	Destabilizing	0.001	N	0.179	neutral	N	0.398801406	None	None	N
I/W	0.7068	likely_pathogenic	0.7795	pathogenic	-1.037	Destabilizing	0.995	D	0.637	neutral	None	None	None	None	N
I/Y	0.3465	ambiguous	0.4068	ambiguous	-0.806	Destabilizing	0.981	D	0.653	neutral	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.