TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18099	54520;54521;54522	chr2:178604794;178604793;178604792	chr2:179469521;179469520;179469519
N2AB	16458	49597;49598;49599	chr2:178604794;178604793;178604792	chr2:179469521;179469520;179469519
N2A	15531	46816;46817;46818	chr2:178604794;178604793;178604792	chr2:179469521;179469520;179469519
N2B	9034	27325;27326;27327	chr2:178604794;178604793;178604792	chr2:179469521;179469520;179469519
Novex-1	9159	27700;27701;27702	chr2:178604794;178604793;178604792	chr2:179469521;179469520;179469519
Novex-2	9226	27901;27902;27903	chr2:178604794;178604793;178604792	chr2:179469521;179469520;179469519
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-19
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.3257
• 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/Q	rs750814326	-0.438	0.891	N	0.564	0.226	0.231231049324	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/Q	rs750814326	-0.438	0.891	N	0.564	0.226	0.231231049324	gnomAD-4.0.0	6.84721E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16036E-05	0
H/Y	None	None	0.961	N	0.546	0.32	0.335661160332	gnomAD-4.0.0	1.59407E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86367E-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	0.6182	likely_pathogenic	0.6748	pathogenic	-1.142	Destabilizing	0.842	D	0.559	neutral	None	None	None	None	N
H/C	0.2473	likely_benign	0.2623	benign	-0.41	Destabilizing	0.998	D	0.619	neutral	None	None	None	None	N
H/D	0.6596	likely_pathogenic	0.6772	pathogenic	-0.806	Destabilizing	0.454	N	0.497	neutral	N	0.430822532	None	None	N
H/E	0.8179	likely_pathogenic	0.8278	pathogenic	-0.687	Destabilizing	0.688	D	0.507	neutral	None	None	None	None	N
H/F	0.557	ambiguous	0.5902	pathogenic	0.14	Stabilizing	0.991	D	0.597	neutral	None	None	None	None	N
H/G	0.4786	ambiguous	0.5285	ambiguous	-1.508	Destabilizing	0.525	D	0.477	neutral	None	None	None	None	N
H/I	0.9041	likely_pathogenic	0.929	pathogenic	-0.116	Destabilizing	0.991	D	0.627	neutral	None	None	None	None	N
H/K	0.7957	likely_pathogenic	0.797	pathogenic	-0.881	Destabilizing	0.842	D	0.515	neutral	None	None	None	None	N
H/L	0.5499	ambiguous	0.6267	pathogenic	-0.116	Destabilizing	0.891	D	0.623	neutral	N	0.473535946	None	None	N
H/M	0.844	likely_pathogenic	0.8779	pathogenic	-0.273	Destabilizing	0.998	D	0.588	neutral	None	None	None	None	N
H/N	0.138	likely_benign	0.1683	benign	-1.02	Destabilizing	0.002	N	0.143	neutral	N	0.368984639	None	None	N
H/P	0.9762	likely_pathogenic	0.9824	pathogenic	-0.44	Destabilizing	0.989	D	0.629	neutral	N	0.46668475	None	None	N
H/Q	0.5651	likely_pathogenic	0.5813	pathogenic	-0.739	Destabilizing	0.891	D	0.564	neutral	N	0.456315622	None	None	N
H/R	0.4742	ambiguous	0.4416	ambiguous	-1.169	Destabilizing	0.801	D	0.477	neutral	N	0.442519606	None	None	N
H/S	0.3259	likely_benign	0.3687	ambiguous	-1.147	Destabilizing	0.525	D	0.469	neutral	None	None	None	None	N
H/T	0.6526	likely_pathogenic	0.6967	pathogenic	-0.929	Destabilizing	0.842	D	0.582	neutral	None	None	None	None	N
H/V	0.8349	likely_pathogenic	0.8652	pathogenic	-0.44	Destabilizing	0.974	D	0.639	neutral	None	None	None	None	N
H/W	0.6864	likely_pathogenic	0.6774	pathogenic	0.467	Stabilizing	0.998	D	0.623	neutral	None	None	None	None	N
H/Y	0.1697	likely_benign	0.1745	benign	0.557	Stabilizing	0.961	D	0.546	neutral	N	0.434670914	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.