TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31035	93328;93329;93330	chr2:178548523;178548522;178548521	chr2:179413250;179413249;179413248
N2AB	29394	88405;88406;88407	chr2:178548523;178548522;178548521	chr2:179413250;179413249;179413248
N2A	28467	85624;85625;85626	chr2:178548523;178548522;178548521	chr2:179413250;179413249;179413248
N2B	21970	66133;66134;66135	chr2:178548523;178548522;178548521	chr2:179413250;179413249;179413248
Novex-1	22095	66508;66509;66510	chr2:178548523;178548522;178548521	chr2:179413250;179413249;179413248
Novex-2	22162	66709;66710;66711	chr2:178548523;178548522;178548521	chr2:179413250;179413249;179413248
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-114
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0923
• 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
L/V	rs760377288	None	0.911	N	0.575	0.265	0.235038932564	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
L/V	rs760377288	None	0.911	N	0.575	0.265	0.235038932564	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-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
L/A	0.9097	likely_pathogenic	0.8504	pathogenic	-2.338	Highly Destabilizing	0.964	D	0.711	prob.delet.	None	None	None	None	N
L/C	0.8926	likely_pathogenic	0.8382	pathogenic	-1.386	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9993	pathogenic	-3.091	Highly Destabilizing	0.998	D	0.868	deleterious	None	None	None	None	N
L/E	0.9979	likely_pathogenic	0.9943	pathogenic	-2.759	Highly Destabilizing	0.998	D	0.852	deleterious	None	None	None	None	N
L/F	0.475	ambiguous	0.3623	ambiguous	-1.434	Destabilizing	0.994	D	0.707	prob.neutral	D	0.542612441	None	None	N
L/G	0.9925	likely_pathogenic	0.9828	pathogenic	-2.941	Highly Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
L/H	0.9933	likely_pathogenic	0.9829	pathogenic	-2.849	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/I	0.1066	likely_benign	0.093	benign	-0.516	Destabilizing	0.469	N	0.343	neutral	None	None	None	None	N
L/K	0.9964	likely_pathogenic	0.9905	pathogenic	-1.753	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
L/M	0.2311	likely_benign	0.1869	benign	-0.666	Destabilizing	0.659	D	0.339	neutral	D	0.522381819	None	None	N
L/N	0.9981	likely_pathogenic	0.9952	pathogenic	-2.546	Highly Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
L/P	0.9961	likely_pathogenic	0.9913	pathogenic	-1.115	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
L/Q	0.9899	likely_pathogenic	0.9744	pathogenic	-2.111	Highly Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
L/R	0.9917	likely_pathogenic	0.9798	pathogenic	-2.043	Highly Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
L/S	0.9927	likely_pathogenic	0.9822	pathogenic	-3.007	Highly Destabilizing	0.961	D	0.773	deleterious	D	0.566592499	None	None	N
L/T	0.9642	likely_pathogenic	0.928	pathogenic	-2.502	Highly Destabilizing	0.469	N	0.595	neutral	None	None	None	None	N
L/V	0.119	likely_benign	0.1043	benign	-1.115	Destabilizing	0.911	D	0.575	neutral	N	0.520351245	None	None	N
L/W	0.9603	likely_pathogenic	0.917	pathogenic	-1.825	Destabilizing	1.0	D	0.858	deleterious	D	0.566592499	None	None	N
L/Y	0.9659	likely_pathogenic	0.9324	pathogenic	-1.588	Destabilizing	0.999	D	0.762	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.