TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21309	64150;64151;64152	chr2:178587286;178587285;178587284	chr2:179452013;179452012;179452011
N2AB	19668	59227;59228;59229	chr2:178587286;178587285;178587284	chr2:179452013;179452012;179452011
N2A	18741	56446;56447;56448	chr2:178587286;178587285;178587284	chr2:179452013;179452012;179452011
N2B	12244	36955;36956;36957	chr2:178587286;178587285;178587284	chr2:179452013;179452012;179452011
Novex-1	12369	37330;37331;37332	chr2:178587286;178587285;178587284	chr2:179452013;179452012;179452011
Novex-2	12436	37531;37532;37533	chr2:178587286;178587285;178587284	chr2:179452013;179452012;179452011
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: Fn3-42
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.369
• 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/H	None	None	0.931	N	0.363	0.297	0.335910606209	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1718	likely_benign	0.1567	benign	-0.071	Destabilizing	0.002	N	0.316	neutral	N	0.499319825	None	None	N
D/C	0.6273	likely_pathogenic	0.5971	pathogenic	-0.031	Destabilizing	0.947	D	0.643	neutral	None	None	None	None	N
D/E	0.1329	likely_benign	0.1245	benign	-0.266	Destabilizing	0.002	N	0.252	neutral	N	0.486889245	None	None	N
D/F	0.6221	likely_pathogenic	0.6018	pathogenic	-0.143	Destabilizing	0.826	D	0.602	neutral	None	None	None	None	N
D/G	0.1609	likely_benign	0.1432	benign	-0.208	Destabilizing	0.201	N	0.31	neutral	N	0.437132429	None	None	N
D/H	0.3758	ambiguous	0.3285	benign	0.315	Stabilizing	0.931	D	0.363	neutral	N	0.474664148	None	None	N
D/I	0.396	ambiguous	0.3707	ambiguous	0.228	Stabilizing	0.7	D	0.606	neutral	None	None	None	None	N
D/K	0.4517	ambiguous	0.3942	ambiguous	0.402	Stabilizing	0.25	N	0.287	neutral	None	None	None	None	N
D/L	0.3611	ambiguous	0.3207	benign	0.228	Stabilizing	0.539	D	0.599	neutral	None	None	None	None	N
D/M	0.5755	likely_pathogenic	0.5485	ambiguous	0.147	Stabilizing	0.982	D	0.631	neutral	None	None	None	None	N
D/N	0.1252	likely_benign	0.1194	benign	0.211	Stabilizing	0.638	D	0.278	neutral	N	0.508685883	None	None	N
D/P	0.7229	likely_pathogenic	0.6864	pathogenic	0.149	Stabilizing	0.826	D	0.361	neutral	None	None	None	None	N
D/Q	0.3518	ambiguous	0.3044	benign	0.206	Stabilizing	0.539	D	0.303	neutral	None	None	None	None	N
D/R	0.518	ambiguous	0.459	ambiguous	0.618	Stabilizing	0.539	D	0.51	neutral	None	None	None	None	N
D/S	0.1276	likely_benign	0.1196	benign	0.092	Stabilizing	0.25	N	0.273	neutral	None	None	None	None	N
D/T	0.2193	likely_benign	0.2093	benign	0.197	Stabilizing	0.7	D	0.307	neutral	None	None	None	None	N
D/V	0.2481	likely_benign	0.2285	benign	0.149	Stabilizing	0.468	N	0.568	neutral	N	0.516020074	None	None	N
D/W	0.8771	likely_pathogenic	0.8541	pathogenic	-0.079	Destabilizing	0.982	D	0.671	neutral	None	None	None	None	N
D/Y	0.3408	ambiguous	0.3067	benign	0.087	Stabilizing	0.976	D	0.6	neutral	N	0.488248953	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.