TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16465	49618;49619;49620	chr2:178613890;178613889;178613888	chr2:179478617;179478616;179478615
N2AB	14824	44695;44696;44697	chr2:178613890;178613889;178613888	chr2:179478617;179478616;179478615
N2A	13897	41914;41915;41916	chr2:178613890;178613889;178613888	chr2:179478617;179478616;179478615
N2B	7400	22423;22424;22425	chr2:178613890;178613889;178613888	chr2:179478617;179478616;179478615
Novex-1	7525	22798;22799;22800	chr2:178613890;178613889;178613888	chr2:179478617;179478616;179478615
Novex-2	7592	22999;23000;23001	chr2:178613890;178613889;178613888	chr2:179478617;179478616;179478615
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-7
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3538
• 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
D/E	None	None	1.0	N	0.438	0.323	0.166414681773	gnomAD-4.0.0	6.85522E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66019E-05

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
D/A	0.7689	likely_pathogenic	0.7554	pathogenic	-0.572	Destabilizing	1.0	D	0.808	deleterious	D	0.541215022	None	None	N
D/C	0.9613	likely_pathogenic	0.9575	pathogenic	-0.075	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
D/E	0.3577	ambiguous	0.305	benign	-0.564	Destabilizing	1.0	D	0.438	neutral	N	0.481717615	None	None	N
D/F	0.9377	likely_pathogenic	0.932	pathogenic	-0.452	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
D/G	0.6788	likely_pathogenic	0.7066	pathogenic	-0.84	Destabilizing	1.0	D	0.756	deleterious	N	0.484186708	None	None	N
D/H	0.8779	likely_pathogenic	0.8679	pathogenic	-0.665	Destabilizing	1.0	D	0.747	deleterious	N	0.475978424	None	None	N
D/I	0.9318	likely_pathogenic	0.9269	pathogenic	0.113	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
D/K	0.9437	likely_pathogenic	0.9427	pathogenic	-0.039	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
D/L	0.9063	likely_pathogenic	0.8968	pathogenic	0.113	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
D/M	0.947	likely_pathogenic	0.937	pathogenic	0.516	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
D/N	0.3633	ambiguous	0.3503	ambiguous	-0.377	Destabilizing	1.0	D	0.598	neutral	N	0.458705987	None	None	N
D/P	0.996	likely_pathogenic	0.9969	pathogenic	-0.092	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
D/Q	0.8927	likely_pathogenic	0.8797	pathogenic	-0.328	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
D/R	0.958	likely_pathogenic	0.958	pathogenic	0.045	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/S	0.5799	likely_pathogenic	0.5679	pathogenic	-0.557	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
D/T	0.7009	likely_pathogenic	0.6628	pathogenic	-0.342	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/V	0.83	likely_pathogenic	0.823	pathogenic	-0.092	Destabilizing	1.0	D	0.803	deleterious	D	0.622495071	None	None	N
D/W	0.9855	likely_pathogenic	0.9872	pathogenic	-0.284	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
D/Y	0.7016	likely_pathogenic	0.7057	pathogenic	-0.208	Destabilizing	1.0	D	0.791	deleterious	D	0.569597526	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.