TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14300	43123;43124;43125	chr2:178633461;178633460;178633459	chr2:179498188;179498187;179498186
N2AB	12659	38200;38201;38202	chr2:178633461;178633460;178633459	chr2:179498188;179498187;179498186
N2A	11732	35419;35420;35421	chr2:178633461;178633460;178633459	chr2:179498188;179498187;179498186
N2B	5235	15928;15929;15930	chr2:178633461;178633460;178633459	chr2:179498188;179498187;179498186
Novex-1	5360	16303;16304;16305	chr2:178633461;178633460;178633459	chr2:179498188;179498187;179498186
Novex-2	5427	16504;16505;16506	chr2:178633461;178633460;178633459	chr2:179498188;179498187;179498186
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-93
• Domain position: 70
• Structural Position: 155
• Q(SASA): 0.1374
• 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
V/L	rs757079194	-0.128	0.004	N	0.459	0.034	0.115124310173	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
V/L	rs757079194	-0.128	0.004	N	0.459	0.034	0.115124310173	gnomAD-4.0.0	1.59229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85971E-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
V/A	0.1409	likely_benign	0.1184	benign	-1.91	Destabilizing	0.012	N	0.421	neutral	N	0.449184211	None	None	N
V/C	0.62	likely_pathogenic	0.578	pathogenic	-1.069	Destabilizing	0.676	D	0.695	prob.neutral	None	None	None	None	N
V/D	0.3252	likely_benign	0.2516	benign	-2.757	Highly Destabilizing	0.038	N	0.715	prob.delet.	None	None	None	None	N
V/E	0.1549	likely_benign	0.1283	benign	-2.457	Highly Destabilizing	None	N	0.492	neutral	N	0.433753689	None	None	N
V/F	0.1595	likely_benign	0.1255	benign	-0.995	Destabilizing	0.214	N	0.727	prob.delet.	None	None	None	None	N
V/G	0.196	likely_benign	0.1746	benign	-2.485	Highly Destabilizing	0.029	N	0.703	prob.neutral	N	0.444681483	None	None	N
V/H	0.4148	ambiguous	0.3823	ambiguous	-2.48	Highly Destabilizing	0.356	N	0.721	prob.delet.	None	None	None	None	N
V/I	0.0762	likely_benign	0.0677	benign	-0.247	Destabilizing	0.016	N	0.539	neutral	None	None	None	None	N
V/K	0.2857	likely_benign	0.2481	benign	-1.285	Destabilizing	0.038	N	0.694	prob.neutral	None	None	None	None	N
V/L	0.139	likely_benign	0.115	benign	-0.247	Destabilizing	0.004	N	0.459	neutral	N	0.449168909	None	None	N
V/M	0.0823	likely_benign	0.0699	benign	-0.437	Destabilizing	0.002	N	0.42	neutral	N	0.451639458	None	None	N
V/N	0.2215	likely_benign	0.1696	benign	-1.887	Destabilizing	0.038	N	0.732	prob.delet.	None	None	None	None	N
V/P	0.9653	likely_pathogenic	0.9585	pathogenic	-0.782	Destabilizing	0.356	N	0.725	prob.delet.	None	None	None	None	N
V/Q	0.1862	likely_benign	0.1677	benign	-1.545	Destabilizing	0.038	N	0.716	prob.delet.	None	None	None	None	N
V/R	0.2571	likely_benign	0.2417	benign	-1.476	Destabilizing	0.214	N	0.748	deleterious	None	None	None	None	N
V/S	0.1318	likely_benign	0.1083	benign	-2.36	Highly Destabilizing	None	N	0.501	neutral	None	None	None	None	N
V/T	0.106	likely_benign	0.0819	benign	-1.914	Destabilizing	None	N	0.242	neutral	None	None	None	None	N
V/W	0.6819	likely_pathogenic	0.6329	pathogenic	-1.602	Destabilizing	0.864	D	0.737	prob.delet.	None	None	None	None	N
V/Y	0.4496	ambiguous	0.3773	ambiguous	-1.218	Destabilizing	0.356	N	0.731	prob.delet.	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.