TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20188	60787;60788;60789	chr2:178591163;178591162;178591161	chr2:179455890;179455889;179455888
N2AB	18547	55864;55865;55866	chr2:178591163;178591162;178591161	chr2:179455890;179455889;179455888
N2A	17620	53083;53084;53085	chr2:178591163;178591162;178591161	chr2:179455890;179455889;179455888
N2B	11123	33592;33593;33594	chr2:178591163;178591162;178591161	chr2:179455890;179455889;179455888
Novex-1	11248	33967;33968;33969	chr2:178591163;178591162;178591161	chr2:179455890;179455889;179455888
Novex-2	11315	34168;34169;34170	chr2:178591163;178591162;178591161	chr2:179455890;179455889;179455888
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: Fn3-34
• Domain position: 18
• Structural Position: 19
• Q(SASA): 0.2092
• 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/R	None	None	0.055	N	0.567	0.119	0.183819452728	gnomAD-4.0.0	1.36877E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79927E-06	0	0
H/Y	None	None	None	N	0.138	0.148	0.0716867268079	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85984E-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	0.2509	likely_benign	0.2451	benign	-0.942	Destabilizing	0.016	N	0.424	neutral	None	None	None	None	N
H/C	0.1223	likely_benign	0.126	benign	-0.278	Destabilizing	0.864	D	0.699	prob.neutral	None	None	None	None	N
H/D	0.2458	likely_benign	0.2542	benign	-1.005	Destabilizing	0.055	N	0.573	neutral	N	0.500335758	None	None	N
H/E	0.2891	likely_benign	0.2807	benign	-0.897	Destabilizing	0.031	N	0.455	neutral	None	None	None	None	N
H/F	0.169	likely_benign	0.1543	benign	0.355	Stabilizing	0.038	N	0.567	neutral	None	None	None	None	N
H/G	0.3088	likely_benign	0.3032	benign	-1.282	Destabilizing	0.031	N	0.459	neutral	None	None	None	None	N
H/I	0.3279	likely_benign	0.3208	benign	0.01	Stabilizing	0.214	N	0.7	prob.neutral	None	None	None	None	N
H/K	0.3139	likely_benign	0.3078	benign	-0.875	Destabilizing	0.072	N	0.543	neutral	None	None	None	None	N
H/L	0.1807	likely_benign	0.1726	benign	0.01	Stabilizing	0.029	N	0.561	neutral	N	0.501029192	None	None	N
H/M	0.3535	ambiguous	0.3325	benign	-0.154	Destabilizing	0.356	N	0.678	prob.neutral	None	None	None	None	N
H/N	0.0898	likely_benign	0.0922	benign	-0.961	Destabilizing	0.055	N	0.469	neutral	N	0.439999375	None	None	N
H/P	0.9063	likely_pathogenic	0.9162	pathogenic	-0.29	Destabilizing	0.295	N	0.681	prob.neutral	N	0.468797891	None	None	N
H/Q	0.1885	likely_benign	0.1858	benign	-0.647	Destabilizing	0.106	N	0.577	neutral	N	0.460219932	None	None	N
H/R	0.1818	likely_benign	0.1801	benign	-1.321	Destabilizing	0.055	N	0.567	neutral	N	0.433092046	None	None	N
H/S	0.1617	likely_benign	0.1563	benign	-0.959	Destabilizing	0.001	N	0.295	neutral	None	None	None	None	N
H/T	0.1928	likely_benign	0.1835	benign	-0.765	Destabilizing	0.038	N	0.522	neutral	None	None	None	None	N
H/V	0.2588	likely_benign	0.2451	benign	-0.29	Destabilizing	0.072	N	0.63	neutral	None	None	None	None	N
H/W	0.3291	likely_benign	0.3009	benign	0.509	Stabilizing	0.676	D	0.667	neutral	None	None	None	None	N
H/Y	0.0598	likely_benign	0.06	benign	0.607	Stabilizing	None	N	0.138	neutral	N	0.399864907	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.