TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24674	74245;74246;74247	chr2:178572112;178572111;178572110	chr2:179436839;179436838;179436837
N2AB	23033	69322;69323;69324	chr2:178572112;178572111;178572110	chr2:179436839;179436838;179436837
N2A	22106	66541;66542;66543	chr2:178572112;178572111;178572110	chr2:179436839;179436838;179436837
N2B	15609	47050;47051;47052	chr2:178572112;178572111;178572110	chr2:179436839;179436838;179436837
Novex-1	15734	47425;47426;47427	chr2:178572112;178572111;178572110	chr2:179436839;179436838;179436837
Novex-2	15801	47626;47627;47628	chr2:178572112;178572111;178572110	chr2:179436839;179436838;179436837
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-67
• Domain position: 59
• Structural Position: 91
• Q(SASA): 0.1365
• 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
A/V	rs1158950009	None	0.663	N	0.449	0.257	0.414930877219	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

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
A/C	0.512	ambiguous	0.5162	ambiguous	-0.741	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
A/D	0.8876	likely_pathogenic	0.8883	pathogenic	-0.753	Destabilizing	0.994	D	0.807	deleterious	N	0.488982968	None	None	N
A/E	0.8134	likely_pathogenic	0.8185	pathogenic	-0.704	Destabilizing	0.997	D	0.727	prob.delet.	None	None	None	None	N
A/F	0.645	likely_pathogenic	0.6475	pathogenic	-0.54	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
A/G	0.2305	likely_benign	0.2363	benign	-0.924	Destabilizing	0.815	D	0.588	neutral	N	0.472600233	None	None	N
A/H	0.8377	likely_pathogenic	0.8343	pathogenic	-1.15	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
A/I	0.5371	ambiguous	0.5643	pathogenic	0.196	Stabilizing	0.991	D	0.699	prob.neutral	None	None	None	None	N
A/K	0.9029	likely_pathogenic	0.9088	pathogenic	-0.872	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
A/L	0.4477	ambiguous	0.4992	ambiguous	0.196	Stabilizing	0.991	D	0.599	neutral	None	None	None	None	N
A/M	0.3883	ambiguous	0.409	ambiguous	-0.004	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
A/N	0.7302	likely_pathogenic	0.7337	pathogenic	-0.807	Destabilizing	0.961	D	0.811	deleterious	None	None	None	None	N
A/P	0.9911	likely_pathogenic	0.9916	pathogenic	-0.021	Destabilizing	0.997	D	0.783	deleterious	N	0.518608113	None	None	N
A/Q	0.7864	likely_pathogenic	0.8029	pathogenic	-0.797	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
A/R	0.8831	likely_pathogenic	0.8921	pathogenic	-0.763	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
A/S	0.2066	likely_benign	0.2077	benign	-1.237	Destabilizing	0.626	D	0.535	neutral	N	0.488640573	None	None	N
A/T	0.1471	likely_benign	0.1416	benign	-1.063	Destabilizing	0.177	N	0.44	neutral	N	0.488121396	None	None	N
A/V	0.2518	likely_benign	0.2712	benign	-0.021	Destabilizing	0.663	D	0.449	neutral	N	0.507125658	None	None	N
A/W	0.953	likely_pathogenic	0.9519	pathogenic	-1.03	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/Y	0.7704	likely_pathogenic	0.7718	pathogenic	-0.503	Destabilizing	1.0	D	0.815	deleterious	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.