TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14306	43141;43142;43143	chr2:178633443;178633442;178633441	chr2:179498170;179498169;179498168
N2AB	12665	38218;38219;38220	chr2:178633443;178633442;178633441	chr2:179498170;179498169;179498168
N2A	11738	35437;35438;35439	chr2:178633443;178633442;178633441	chr2:179498170;179498169;179498168
N2B	5241	15946;15947;15948	chr2:178633443;178633442;178633441	chr2:179498170;179498169;179498168
Novex-1	5366	16321;16322;16323	chr2:178633443;178633442;178633441	chr2:179498170;179498169;179498168
Novex-2	5433	16522;16523;16524	chr2:178633443;178633442;178633441	chr2:179498170;179498169;179498168
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: Ig-93
• Domain position: 76
• Structural Position: 162
• Q(SASA): 0.3293
• 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	rs537375897	-0.342	1.0	N	0.477	0.201	0.326616659874	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
D/E	rs537375897	-0.342	1.0	N	0.477	0.201	0.326616659874	gnomAD-4.0.0	2.73759E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99617E-07	3.47866E-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
D/A	0.5007	ambiguous	0.309	benign	-0.628	Destabilizing	1.0	D	0.756	deleterious	N	0.505953922	None	None	N
D/C	0.9361	likely_pathogenic	0.854	pathogenic	-0.266	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
D/E	0.4514	ambiguous	0.3211	benign	-0.782	Destabilizing	1.0	D	0.477	neutral	N	0.507610107	None	None	N
D/F	0.9183	likely_pathogenic	0.8433	pathogenic	-0.38	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
D/G	0.5111	ambiguous	0.3688	ambiguous	-0.982	Destabilizing	1.0	D	0.701	prob.neutral	D	0.552761374	None	None	N
D/H	0.7401	likely_pathogenic	0.6162	pathogenic	-0.779	Destabilizing	1.0	D	0.702	prob.neutral	D	0.685051691	None	None	N
D/I	0.867	likely_pathogenic	0.7155	pathogenic	0.307	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
D/K	0.8479	likely_pathogenic	0.7314	pathogenic	-0.547	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
D/L	0.8524	likely_pathogenic	0.7336	pathogenic	0.307	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
D/M	0.9389	likely_pathogenic	0.8714	pathogenic	0.814	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
D/N	0.2277	likely_benign	0.1606	benign	-0.909	Destabilizing	1.0	D	0.685	prob.neutral	D	0.55275671	None	None	N
D/P	0.9842	likely_pathogenic	0.9776	pathogenic	0.02	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
D/Q	0.7613	likely_pathogenic	0.6322	pathogenic	-0.77	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
D/R	0.8625	likely_pathogenic	0.7765	pathogenic	-0.444	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
D/S	0.3187	likely_benign	0.2135	benign	-1.198	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
D/T	0.6751	likely_pathogenic	0.4848	ambiguous	-0.91	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
D/V	0.6712	likely_pathogenic	0.4618	ambiguous	0.02	Stabilizing	1.0	D	0.779	deleterious	N	0.503309007	None	None	N
D/W	0.9867	likely_pathogenic	0.9775	pathogenic	-0.26	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
D/Y	0.6739	likely_pathogenic	0.5148	ambiguous	-0.159	Destabilizing	1.0	D	0.755	deleterious	D	0.646431924	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.