TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10040	30343;30344;30345	chr2:178704252;178704251;178704250	chr2:179568979;179568978;179568977
N2AB	9723	29392;29393;29394	chr2:178704252;178704251;178704250	chr2:179568979;179568978;179568977
N2A	8796	26611;26612;26613	chr2:178704252;178704251;178704250	chr2:179568979;179568978;179568977
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-85
• Domain position: 52
• Structural Position: 131
• Q(SASA): 0.4825
• 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
H/Y	None	None	0.051	None	0.153	0.177	0.166414681773	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
H/A	0.4827	ambiguous	0.5554	ambiguous	0.31	Stabilizing	0.842	D	0.295	neutral	None	None	None	None	N
H/C	0.4766	ambiguous	0.5502	ambiguous	0.833	Stabilizing	0.998	D	0.419	neutral	None	None	None	None	N
H/D	0.1563	likely_benign	0.1886	benign	-0.008	Destabilizing	0.012	N	0.192	neutral	None	None	None	None	N
H/E	0.3293	likely_benign	0.3912	ambiguous	0.014	Stabilizing	0.016	N	0.137	neutral	None	None	None	None	N
H/F	0.551	ambiguous	0.591	pathogenic	0.903	Stabilizing	0.904	D	0.359	neutral	None	None	None	None	N
H/G	0.3223	likely_benign	0.3796	ambiguous	0.025	Stabilizing	0.842	D	0.303	neutral	None	None	None	None	N
H/I	0.7679	likely_pathogenic	0.8164	pathogenic	1.037	Stabilizing	0.974	D	0.403	neutral	None	None	None	None	N
H/K	0.3748	ambiguous	0.3925	ambiguous	0.255	Stabilizing	0.728	D	0.258	neutral	None	None	None	None	N
H/L	0.2651	likely_benign	0.3042	benign	1.037	Stabilizing	0.801	D	0.337	neutral	None	None	None	None	N
H/M	0.694	likely_pathogenic	0.759	pathogenic	0.836	Stabilizing	0.998	D	0.365	neutral	None	None	None	None	N
H/N	0.078	likely_benign	0.0901	benign	0.329	Stabilizing	0.669	D	0.279	neutral	None	None	None	None	N
H/P	0.3807	ambiguous	0.4295	ambiguous	0.821	Stabilizing	0.966	D	0.385	neutral	None	None	None	None	N
H/Q	0.2528	likely_benign	0.2908	benign	0.426	Stabilizing	0.669	D	0.355	neutral	None	None	None	None	N
H/R	0.1994	likely_benign	0.2094	benign	-0.357	Destabilizing	0.801	D	0.344	neutral	None	None	None	None	N
H/S	0.3201	likely_benign	0.3719	ambiguous	0.449	Stabilizing	0.842	D	0.285	neutral	None	None	None	None	N
H/T	0.487	ambiguous	0.5639	ambiguous	0.567	Stabilizing	0.842	D	0.323	neutral	None	None	None	None	N
H/V	0.6687	likely_pathogenic	0.7256	pathogenic	0.821	Stabilizing	0.842	D	0.375	neutral	None	None	None	None	N
H/W	0.6496	likely_pathogenic	0.6806	pathogenic	0.87	Stabilizing	0.993	D	0.369	neutral	None	None	None	None	N
H/Y	0.1586	likely_benign	0.1758	benign	1.179	Stabilizing	0.051	N	0.153	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.