TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15724	47395;47396;47397	chr2:178618288;178618287;178618286	chr2:179483015;179483014;179483013
N2AB	14083	42472;42473;42474	chr2:178618288;178618287;178618286	chr2:179483015;179483014;179483013
N2A	13156	39691;39692;39693	chr2:178618288;178618287;178618286	chr2:179483015;179483014;179483013
N2B	6659	20200;20201;20202	chr2:178618288;178618287;178618286	chr2:179483015;179483014;179483013
Novex-1	6784	20575;20576;20577	chr2:178618288;178618287;178618286	chr2:179483015;179483014;179483013
Novex-2	6851	20776;20777;20778	chr2:178618288;178618287;178618286	chr2:179483015;179483014;179483013
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-1
• Domain position: 68
• Structural Position: 100
• Q(SASA): 0.4871
• 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
G/A	None	None	0.999	N	0.649	0.374	0.256283259241	gnomAD-4.0.0	2.05379E-06	None	None	None	None	N	None	0	0	None	0	2.52525E-05	None	0	1.73853E-04	8.99875E-07	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
G/A	0.1943	likely_benign	0.164	benign	-0.389	Destabilizing	0.999	D	0.649	neutral	N	0.473343651	None	None	N
G/C	0.4268	ambiguous	0.335	benign	-0.982	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
G/D	0.3163	likely_benign	0.3201	benign	-0.624	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
G/E	0.3735	ambiguous	0.3528	ambiguous	-0.786	Destabilizing	1.0	D	0.784	deleterious	N	0.475107423	None	None	N
G/F	0.772	likely_pathogenic	0.7503	pathogenic	-1.033	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/H	0.6187	likely_pathogenic	0.5634	ambiguous	-0.519	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
G/I	0.5934	likely_pathogenic	0.5433	ambiguous	-0.522	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
G/K	0.7044	likely_pathogenic	0.6794	pathogenic	-0.904	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
G/L	0.654	likely_pathogenic	0.5897	pathogenic	-0.522	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
G/M	0.6775	likely_pathogenic	0.6392	pathogenic	-0.588	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
G/N	0.3192	likely_benign	0.2869	benign	-0.561	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
G/P	0.8366	likely_pathogenic	0.7354	pathogenic	-0.445	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/Q	0.5326	ambiguous	0.4863	ambiguous	-0.863	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
G/R	0.616	likely_pathogenic	0.581	pathogenic	-0.41	Destabilizing	1.0	D	0.809	deleterious	N	0.476705519	None	None	N
G/S	0.1481	likely_benign	0.1366	benign	-0.723	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
G/T	0.2639	likely_benign	0.2131	benign	-0.816	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
G/V	0.4009	ambiguous	0.3505	ambiguous	-0.445	Destabilizing	1.0	D	0.767	deleterious	D	0.574308493	None	None	N
G/W	0.6096	likely_pathogenic	0.5972	pathogenic	-1.151	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/Y	0.6144	likely_pathogenic	0.5833	pathogenic	-0.827	Destabilizing	1.0	D	0.81	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.