TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32757	98494;98495;98496	chr2:178539796;178539795;178539794	chr2:179404523;179404522;179404521
N2AB	31116	93571;93572;93573	chr2:178539796;178539795;178539794	chr2:179404523;179404522;179404521
N2A	30189	90790;90791;90792	chr2:178539796;178539795;178539794	chr2:179404523;179404522;179404521
N2B	23692	71299;71300;71301	chr2:178539796;178539795;178539794	chr2:179404523;179404522;179404521
Novex-1	23817	71674;71675;71676	chr2:178539796;178539795;178539794	chr2:179404523;179404522;179404521
Novex-2	23884	71875;71876;71877	chr2:178539796;178539795;178539794	chr2:179404523;179404522;179404521
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-155
• Domain position: 50
• Structural Position: 135
• Q(SASA): 0.4319
• 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/N	rs1438849988	-0.333	0.912	N	0.285	0.222	0.42886291518	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
H/N	rs1438849988	-0.333	0.912	N	0.285	0.222	0.42886291518	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/N	rs1438849988	-0.333	0.912	N	0.285	0.222	0.42886291518	gnomAD-4.0.0	3.0449E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61476E-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	0.2473	likely_benign	0.2581	benign	-0.578	Destabilizing	0.737	D	0.463	neutral	None	None	None	None	N
H/C	0.165	likely_benign	0.1673	benign	0.043	Stabilizing	0.998	D	0.506	neutral	None	None	None	None	N
H/D	0.2839	likely_benign	0.2996	benign	-0.336	Destabilizing	0.912	D	0.487	neutral	N	0.449920873	None	None	N
H/E	0.291	likely_benign	0.3049	benign	-0.3	Destabilizing	0.872	D	0.241	neutral	None	None	None	None	N
H/F	0.2605	likely_benign	0.2737	benign	-0.168	Destabilizing	0.872	D	0.481	neutral	None	None	None	None	N
H/G	0.3416	ambiguous	0.3689	ambiguous	-0.862	Destabilizing	0.932	D	0.517	neutral	None	None	None	None	N
H/I	0.2948	likely_benign	0.3117	benign	0.167	Stabilizing	0.037	N	0.261	neutral	None	None	None	None	N
H/K	0.2615	likely_benign	0.2734	benign	-0.511	Destabilizing	0.773	D	0.441	neutral	None	None	None	None	N
H/L	0.1505	likely_benign	0.1596	benign	0.167	Stabilizing	0.007	N	0.262	neutral	N	0.471085579	None	None	N
H/M	0.3627	ambiguous	0.3745	ambiguous	0.155	Stabilizing	0.96	D	0.51	neutral	None	None	None	None	N
H/N	0.1074	likely_benign	0.1138	benign	-0.304	Destabilizing	0.912	D	0.285	neutral	N	0.477934193	None	None	N
H/P	0.8558	likely_pathogenic	0.8852	pathogenic	-0.059	Destabilizing	0.991	D	0.513	neutral	D	0.535078342	None	None	N
H/Q	0.1606	likely_benign	0.1636	benign	-0.226	Destabilizing	0.837	D	0.369	neutral	N	0.496866671	None	None	N
H/R	0.122	likely_benign	0.1282	benign	-0.709	Destabilizing	0.016	N	0.201	neutral	N	0.446611209	None	None	N
H/S	0.1897	likely_benign	0.1975	benign	-0.41	Destabilizing	0.932	D	0.433	neutral	None	None	None	None	N
H/T	0.211	likely_benign	0.2241	benign	-0.289	Destabilizing	0.932	D	0.492	neutral	None	None	None	None	N
H/V	0.2219	likely_benign	0.234	benign	-0.059	Destabilizing	0.584	D	0.468	neutral	None	None	None	None	N
H/W	0.3995	ambiguous	0.3993	ambiguous	-0.101	Destabilizing	0.998	D	0.495	neutral	None	None	None	None	N
H/Y	0.1033	likely_benign	0.1059	benign	0.278	Stabilizing	0.969	D	0.319	neutral	N	0.465949118	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.