TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30147	90664;90665;90666	chr2:178552461;178552460;178552459	chr2:179417188;179417187;179417186
N2AB	28506	85741;85742;85743	chr2:178552461;178552460;178552459	chr2:179417188;179417187;179417186
N2A	27579	82960;82961;82962	chr2:178552461;178552460;178552459	chr2:179417188;179417187;179417186
N2B	21082	63469;63470;63471	chr2:178552461;178552460;178552459	chr2:179417188;179417187;179417186
Novex-1	21207	63844;63845;63846	chr2:178552461;178552460;178552459	chr2:179417188;179417187;179417186
Novex-2	21274	64045;64046;64047	chr2:178552461;178552460;178552459	chr2:179417188;179417187;179417186
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-148
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.5958
• 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
H/Q	rs72648242	0.526	0.062	N	0.129	0.071	0.117506650769	gnomAD-2.1.1	1.62E-05	None	None	None	None	I	None	0	1.16381E-04	None	0	0	None	0	None	0	0	0
H/Q	rs72648242	0.526	0.062	N	0.129	0.071	0.117506650769	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	1.47E-05	0	0
H/Q	rs72648242	0.526	0.062	N	0.129	0.071	0.117506650769	gnomAD-4.0.0	1.28951E-05	None	None	None	None	I	None	0	1.52864E-04	None	0	0	None	0	0	2.41611E-06	0	0
H/Y	None	None	0.012	N	0.177	0.132	0.137902524267	gnomAD-4.0.0	1.60242E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.88672E-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	0.4645	ambiguous	0.3583	ambiguous	0.307	Stabilizing	0.688	D	0.307	neutral	None	None	None	None	I
H/C	0.3119	likely_benign	0.2313	benign	0.849	Stabilizing	0.998	D	0.341	neutral	None	None	None	None	I
H/D	0.3593	ambiguous	0.2542	benign	0.168	Stabilizing	0.801	D	0.3	neutral	N	0.404083356	None	None	I
H/E	0.4393	ambiguous	0.3323	benign	0.182	Stabilizing	0.525	D	0.299	neutral	None	None	None	None	I
H/F	0.5125	ambiguous	0.4344	ambiguous	0.769	Stabilizing	0.728	D	0.323	neutral	None	None	None	None	I
H/G	0.455	ambiguous	0.3482	ambiguous	0.032	Stabilizing	0.915	D	0.349	neutral	None	None	None	None	I
H/I	0.6361	likely_pathogenic	0.5293	ambiguous	0.999	Stabilizing	0.949	D	0.377	neutral	None	None	None	None	I
H/K	0.3921	ambiguous	0.3038	benign	0.337	Stabilizing	0.728	D	0.291	neutral	None	None	None	None	I
H/L	0.2695	likely_benign	0.2325	benign	0.999	Stabilizing	0.669	D	0.371	neutral	N	0.476063671	None	None	I
H/M	0.6178	likely_pathogenic	0.5218	ambiguous	0.861	Stabilizing	0.991	D	0.331	neutral	None	None	None	None	I
H/N	0.125	likely_benign	0.0967	benign	0.47	Stabilizing	0.891	D	0.269	neutral	N	0.44289246	None	None	I
H/P	0.7462	likely_pathogenic	0.66	pathogenic	0.795	Stabilizing	0.989	D	0.364	neutral	N	0.483432361	None	None	I
H/Q	0.2149	likely_benign	0.1727	benign	0.534	Stabilizing	0.062	N	0.129	neutral	N	0.39003941	None	None	I
H/R	0.2178	likely_benign	0.1762	benign	-0.187	Destabilizing	0.801	D	0.231	neutral	N	0.439372152	None	None	I
H/S	0.3064	likely_benign	0.2254	benign	0.516	Stabilizing	0.842	D	0.289	neutral	None	None	None	None	I
H/T	0.426	ambiguous	0.32	benign	0.626	Stabilizing	0.915	D	0.388	neutral	None	None	None	None	I
H/V	0.5213	ambiguous	0.4185	ambiguous	0.795	Stabilizing	0.842	D	0.401	neutral	None	None	None	None	I
H/W	0.6483	likely_pathogenic	0.5513	ambiguous	0.726	Stabilizing	0.993	D	0.327	neutral	None	None	None	None	I
H/Y	0.1789	likely_benign	0.1461	benign	1.086	Stabilizing	0.012	N	0.177	neutral	N	0.465019958	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.