TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8219	24880;24881;24882	chr2:178718451;178718450;178718449	chr2:179583178;179583177;179583176
N2AB	7902	23929;23930;23931	chr2:178718451;178718450;178718449	chr2:179583178;179583177;179583176
N2A	6975	21148;21149;21150	chr2:178718451;178718450;178718449	chr2:179583178;179583177;179583176
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-67
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.377
• 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
I/T	None	None	0.003	D	0.251	0.384	0.693211236521	gnomAD-4.0.0	1.59135E-06	None	None	None	None	I	None	0	2.28666E-05	None	0	0	None	0	0	0	0	0
I/V	rs766216038	-1.13	None	N	0.156	0.122	0.503744809241	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs766216038	-1.13	None	N	0.156	0.122	0.503744809241	gnomAD-4.0.0	3.18271E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85848E-06	1.43275E-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
I/A	0.5526	ambiguous	0.6036	pathogenic	-2.027	Highly Destabilizing	0.025	N	0.287	neutral	None	None	None	None	I
I/C	0.7941	likely_pathogenic	0.8002	pathogenic	-1.292	Destabilizing	0.859	D	0.521	neutral	None	None	None	None	I
I/D	0.8871	likely_pathogenic	0.9149	pathogenic	-1.667	Destabilizing	0.22	N	0.599	neutral	None	None	None	None	I
I/E	0.7186	likely_pathogenic	0.7637	pathogenic	-1.609	Destabilizing	0.22	N	0.548	neutral	None	None	None	None	I
I/F	0.1716	likely_benign	0.1773	benign	-1.449	Destabilizing	0.001	N	0.226	neutral	N	0.50677646	None	None	I
I/G	0.8386	likely_pathogenic	0.8747	pathogenic	-2.427	Highly Destabilizing	0.22	N	0.492	neutral	None	None	None	None	I
I/H	0.6604	likely_pathogenic	0.6824	pathogenic	-1.75	Destabilizing	0.859	D	0.565	neutral	None	None	None	None	I
I/K	0.51	ambiguous	0.5481	ambiguous	-1.396	Destabilizing	0.22	N	0.547	neutral	None	None	None	None	I
I/L	0.1421	likely_benign	0.1497	benign	-0.962	Destabilizing	None	N	0.105	neutral	D	0.530115239	None	None	I
I/M	0.1142	likely_benign	0.1235	benign	-0.723	Destabilizing	0.019	N	0.241	neutral	D	0.533944978	None	None	I
I/N	0.4661	ambiguous	0.539	ambiguous	-1.292	Destabilizing	0.175	N	0.637	neutral	D	0.533403092	None	None	I
I/P	0.9319	likely_pathogenic	0.9444	pathogenic	-1.288	Destabilizing	0.001	N	0.373	neutral	None	None	None	None	I
I/Q	0.581	likely_pathogenic	0.6117	pathogenic	-1.408	Destabilizing	0.667	D	0.625	neutral	None	None	None	None	I
I/R	0.418	ambiguous	0.4533	ambiguous	-0.87	Destabilizing	0.497	N	0.63	neutral	None	None	None	None	I
I/S	0.5089	ambiguous	0.5941	pathogenic	-1.958	Destabilizing	0.008	N	0.377	neutral	N	0.521286318	None	None	I
I/T	0.4153	ambiguous	0.4668	ambiguous	-1.771	Destabilizing	0.003	N	0.251	neutral	D	0.526904363	None	None	I
I/V	0.0851	likely_benign	0.0831	benign	-1.288	Destabilizing	None	N	0.156	neutral	N	0.500866981	None	None	I
I/W	0.7951	likely_pathogenic	0.7906	pathogenic	-1.612	Destabilizing	0.958	D	0.579	neutral	None	None	None	None	I
I/Y	0.5197	ambiguous	0.5413	ambiguous	-1.366	Destabilizing	0.124	N	0.582	neutral	None	None	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.