TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18681	56266;56267;56268	chr2:178600863;178600862;178600861	chr2:179465590;179465589;179465588
N2AB	17040	51343;51344;51345	chr2:178600863;178600862;178600861	chr2:179465590;179465589;179465588
N2A	16113	48562;48563;48564	chr2:178600863;178600862;178600861	chr2:179465590;179465589;179465588
N2B	9616	29071;29072;29073	chr2:178600863;178600862;178600861	chr2:179465590;179465589;179465588
Novex-1	9741	29446;29447;29448	chr2:178600863;178600862;178600861	chr2:179465590;179465589;179465588
Novex-2	9808	29647;29648;29649	chr2:178600863;178600862;178600861	chr2:179465590;179465589;179465588
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: Fn3-23
• Domain position: 103
• Structural Position: 132
• Q(SASA): 0.8682
• 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/Y	None	None	None	N	None	0.465	None	gnomAD-4.0.0	1.59355E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86288E-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	0.5944	likely_pathogenic	0.4854	ambiguous	-0.301	Destabilizing	None	None	None	None	N	0.503815994	None	None	N
D/C	0.9327	likely_pathogenic	0.9108	pathogenic	-0.087	Destabilizing	None	None	None	None	None	None	None	None	N
D/E	0.3951	ambiguous	0.3419	ambiguous	-0.282	Destabilizing	None	None	None	None	N	0.470935571	None	None	N
D/F	0.9281	likely_pathogenic	0.8942	pathogenic	-0.175	Destabilizing	None	None	None	None	None	None	None	None	N
D/G	0.6153	likely_pathogenic	0.5174	ambiguous	-0.503	Destabilizing	None	None	None	None	N	0.476440758	None	None	N
D/H	0.8055	likely_pathogenic	0.7576	pathogenic	0.016	Stabilizing	None	None	None	None	N	0.482698637	None	None	N
D/I	0.8737	likely_pathogenic	0.8228	pathogenic	0.185	Stabilizing	None	None	None	None	None	None	None	None	N
D/K	0.8955	likely_pathogenic	0.8685	pathogenic	0.24	Stabilizing	None	None	None	None	None	None	None	None	N
D/L	0.8245	likely_pathogenic	0.7629	pathogenic	0.185	Stabilizing	None	None	None	None	None	None	None	None	N
D/M	0.9298	likely_pathogenic	0.902	pathogenic	0.257	Stabilizing	None	None	None	None	None	None	None	None	N
D/N	0.3365	likely_benign	0.273	benign	-0.099	Destabilizing	None	None	None	None	N	0.475999913	None	None	N
D/P	0.8692	likely_pathogenic	0.8244	pathogenic	0.045	Stabilizing	None	None	None	None	None	None	None	None	N
D/Q	0.8222	likely_pathogenic	0.7761	pathogenic	-0.058	Destabilizing	None	None	None	None	None	None	None	None	N
D/R	0.9122	likely_pathogenic	0.8892	pathogenic	0.446	Stabilizing	0.991	D	0.599	neutral	None	None	None	None	N
D/S	0.5024	ambiguous	0.4141	ambiguous	-0.213	Destabilizing	None	None	None	None	None	None	None	None	N
D/T	0.7915	likely_pathogenic	0.7339	pathogenic	-0.054	Destabilizing	None	None	None	None	None	None	None	None	N
D/V	0.7053	likely_pathogenic	0.6248	pathogenic	0.045	Stabilizing	None	None	None	None	N	0.486991051	None	None	N
D/W	0.9822	likely_pathogenic	0.977	pathogenic	-0.029	Destabilizing	None	None	None	None	None	None	None	None	N
D/Y	0.6174	likely_pathogenic	0.5487	ambiguous	0.059	Stabilizing	None	None	None	None	N	0.509703662	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.