TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14239	42940;42941;42942	chr2:178633644;178633643;178633642	chr2:179498371;179498370;179498369
N2AB	12598	38017;38018;38019	chr2:178633644;178633643;178633642	chr2:179498371;179498370;179498369
N2A	11671	35236;35237;35238	chr2:178633644;178633643;178633642	chr2:179498371;179498370;179498369
N2B	5174	15745;15746;15747	chr2:178633644;178633643;178633642	chr2:179498371;179498370;179498369
Novex-1	5299	16120;16121;16122	chr2:178633644;178633643;178633642	chr2:179498371;179498370;179498369
Novex-2	5366	16321;16322;16323	chr2:178633644;178633643;178633642	chr2:179498371;179498370;179498369
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: 9
• Structural Position: 11
• Q(SASA): 0.5234
• 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/N	rs1050740085	None	1.0	N	0.611	0.305	0.239305524855	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-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	0.4889	ambiguous	0.3655	ambiguous	-0.135	Destabilizing	1.0	D	0.753	deleterious	D	0.570942855	None	None	N
D/C	0.9061	likely_pathogenic	0.8419	pathogenic	0.154	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
D/E	0.3946	ambiguous	0.317	benign	-0.292	Destabilizing	1.0	D	0.434	neutral	D	0.550699244	None	None	N
D/F	0.9487	likely_pathogenic	0.8934	pathogenic	-0.243	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
D/G	0.3534	ambiguous	0.2541	benign	-0.312	Destabilizing	1.0	D	0.742	deleterious	D	0.613323011	None	None	N
D/H	0.6389	likely_pathogenic	0.5199	ambiguous	-0.117	Destabilizing	1.0	D	0.695	prob.neutral	D	0.578548968	None	None	N
D/I	0.8847	likely_pathogenic	0.7743	pathogenic	0.273	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
D/K	0.788	likely_pathogenic	0.669	pathogenic	0.341	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
D/L	0.8758	likely_pathogenic	0.7667	pathogenic	0.273	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
D/M	0.9485	likely_pathogenic	0.9015	pathogenic	0.393	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
D/N	0.1373	likely_benign	0.1051	benign	0.182	Stabilizing	1.0	D	0.611	neutral	N	0.45203435	None	None	N
D/P	0.6788	likely_pathogenic	0.6565	pathogenic	0.159	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
D/Q	0.7083	likely_pathogenic	0.6078	pathogenic	0.195	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
D/R	0.8206	likely_pathogenic	0.7091	pathogenic	0.446	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
D/S	0.2362	likely_benign	0.1724	benign	0.066	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	N
D/T	0.5629	ambiguous	0.4609	ambiguous	0.195	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
D/V	0.7569	likely_pathogenic	0.5986	pathogenic	0.159	Stabilizing	1.0	D	0.784	deleterious	D	0.541843204	None	None	N
D/W	0.9849	likely_pathogenic	0.9764	pathogenic	-0.189	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
D/Y	0.7094	likely_pathogenic	0.5406	ambiguous	-0.025	Destabilizing	1.0	D	0.765	deleterious	D	0.63002378	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.