TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32465	97618;97619;97620	chr2:178542363;178542362;178542361	chr2:179407090;179407089;179407088
N2AB	30824	92695;92696;92697	chr2:178542363;178542362;178542361	chr2:179407090;179407089;179407088
N2A	29897	89914;89915;89916	chr2:178542363;178542362;178542361	chr2:179407090;179407089;179407088
N2B	23400	70423;70424;70425	chr2:178542363;178542362;178542361	chr2:179407090;179407089;179407088
Novex-1	23525	70798;70799;70800	chr2:178542363;178542362;178542361	chr2:179407090;179407089;179407088
Novex-2	23592	70999;71000;71001	chr2:178542363;178542362;178542361	chr2:179407090;179407089;179407088
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-124
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.31
• 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
T/A	rs753202914	-0.837	0.012	N	0.246	0.122	0.137902524267	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/A	rs753202914	-0.837	0.012	N	0.246	0.122	0.137902524267	gnomAD-4.0.0	1.59167E-06	None	None	None	None	N	None	0	2.28686E-05	None	0	0	None	0	0	0	0	0
T/I	None	None	None	N	0.167	0.118	0.104622674875	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/S	None	None	0.002	N	0.123	0.096	0.0482279557977	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
T/A	0.0869	likely_benign	0.0785	benign	-0.926	Destabilizing	0.012	N	0.246	neutral	N	0.469647265	None	None	N
T/C	0.3517	ambiguous	0.3024	benign	-0.448	Destabilizing	0.864	D	0.37	neutral	None	None	None	None	N
T/D	0.4561	ambiguous	0.4188	ambiguous	-0.08	Destabilizing	0.038	N	0.341	neutral	None	None	None	None	N
T/E	0.2954	likely_benign	0.2864	benign	-0.108	Destabilizing	0.072	N	0.351	neutral	None	None	None	None	N
T/F	0.2506	likely_benign	0.1984	benign	-1.198	Destabilizing	0.214	N	0.438	neutral	None	None	None	None	N
T/G	0.2489	likely_benign	0.2164	benign	-1.139	Destabilizing	0.072	N	0.391	neutral	None	None	None	None	N
T/H	0.2481	likely_benign	0.2166	benign	-1.406	Destabilizing	0.356	N	0.401	neutral	None	None	None	None	N
T/I	0.0885	likely_benign	0.0774	benign	-0.459	Destabilizing	None	N	0.167	neutral	N	0.469996995	None	None	N
T/K	0.2069	likely_benign	0.2066	benign	-0.638	Destabilizing	0.072	N	0.357	neutral	None	None	None	None	N
T/L	0.0773	likely_benign	0.0679	benign	-0.459	Destabilizing	0.002	N	0.285	neutral	None	None	None	None	N
T/M	0.0763	likely_benign	0.0709	benign	-0.03	Destabilizing	0.007	N	0.277	neutral	None	None	None	None	N
T/N	0.1222	likely_benign	0.1051	benign	-0.509	Destabilizing	0.001	N	0.185	neutral	N	0.468842202	None	None	N
T/P	0.3299	likely_benign	0.275	benign	-0.584	Destabilizing	0.295	N	0.406	neutral	N	0.48104325	None	None	N
T/Q	0.1954	likely_benign	0.1903	benign	-0.732	Destabilizing	0.356	N	0.399	neutral	None	None	None	None	N
T/R	0.1965	likely_benign	0.1845	benign	-0.341	Destabilizing	0.356	N	0.405	neutral	None	None	None	None	N
T/S	0.117	likely_benign	0.1038	benign	-0.817	Destabilizing	0.002	N	0.123	neutral	N	0.500549189	None	None	N
T/V	0.0847	likely_benign	0.0744	benign	-0.584	Destabilizing	None	N	0.063	neutral	None	None	None	None	N
T/W	0.5921	likely_pathogenic	0.5043	ambiguous	-1.095	Destabilizing	0.864	D	0.42	neutral	None	None	None	None	N
T/Y	0.3091	likely_benign	0.2682	benign	-0.87	Destabilizing	0.356	N	0.433	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.