TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4621	14086;14087;14088	chr2:178739372;178739371;178739370	chr2:179604099;179604098;179604097
N2AB	4304	13135;13136;13137	chr2:178739372;178739371;178739370	chr2:179604099;179604098;179604097
N2A	None	None	chr2:None	chr2:None
N2B	4258	12997;12998;12999	chr2:178739372;178739371;178739370	chr2:179604099;179604098;179604097
Novex-1	4383	13372;13373;13374	chr2:178739372;178739371;178739370	chr2:179604099;179604098;179604097
Novex-2	4450	13573;13574;13575	chr2:178739372;178739371;178739370	chr2:179604099;179604098;179604097
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-29
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2693
• 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/G	None	None	0.003	N	0.163	0.089	0.226586394389	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85802E-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
D/A	0.1448	likely_benign	0.1262	benign	-0.696	Destabilizing	0.309	N	0.349	neutral	N	0.494765878	None	None	N
D/C	0.4205	ambiguous	0.3842	ambiguous	-0.155	Destabilizing	0.996	D	0.441	neutral	None	None	None	None	N
D/E	0.1722	likely_benign	0.1556	benign	-0.544	Destabilizing	0.007	N	0.226	neutral	N	0.444264531	None	None	N
D/F	0.4571	ambiguous	0.4061	ambiguous	-0.536	Destabilizing	0.984	D	0.436	neutral	None	None	None	None	N
D/G	0.1138	likely_benign	0.1048	benign	-0.948	Destabilizing	0.003	N	0.163	neutral	N	0.453054522	None	None	N
D/H	0.2031	likely_benign	0.1833	benign	-0.632	Destabilizing	0.939	D	0.335	neutral	N	0.487917474	None	None	N
D/I	0.3499	ambiguous	0.2989	benign	-0.058	Destabilizing	0.953	D	0.457	neutral	None	None	None	None	N
D/K	0.2629	likely_benign	0.2423	benign	-0.047	Destabilizing	0.59	D	0.321	neutral	None	None	None	None	N
D/L	0.3735	ambiguous	0.3187	benign	-0.058	Destabilizing	0.742	D	0.443	neutral	None	None	None	None	N
D/M	0.5177	ambiguous	0.4635	ambiguous	0.314	Stabilizing	0.996	D	0.424	neutral	None	None	None	None	N
D/N	0.0828	likely_benign	0.0773	benign	-0.426	Destabilizing	0.007	N	0.309	neutral	N	0.436207575	None	None	N
D/P	0.8432	likely_pathogenic	0.8082	pathogenic	-0.248	Destabilizing	0.953	D	0.351	neutral	None	None	None	None	N
D/Q	0.2543	likely_benign	0.2291	benign	-0.386	Destabilizing	0.835	D	0.325	neutral	None	None	None	None	N
D/R	0.2848	likely_benign	0.2616	benign	0.087	Stabilizing	0.91	D	0.427	neutral	None	None	None	None	N
D/S	0.0987	likely_benign	0.09	benign	-0.581	Destabilizing	0.016	N	0.124	neutral	None	None	None	None	N
D/T	0.22	likely_benign	0.1892	benign	-0.38	Destabilizing	0.59	D	0.329	neutral	None	None	None	None	N
D/V	0.2282	likely_benign	0.1967	benign	-0.248	Destabilizing	0.939	D	0.449	neutral	D	0.565248807	None	None	N
D/W	0.7938	likely_pathogenic	0.7699	pathogenic	-0.328	Destabilizing	0.996	D	0.553	neutral	None	None	None	None	N
D/Y	0.1683	likely_benign	0.1569	benign	-0.289	Destabilizing	0.979	D	0.437	neutral	N	0.441021868	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.