TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21032	63319;63320;63321	chr2:178588631;178588630;178588629	chr2:179453358;179453357;179453356
N2AB	19391	58396;58397;58398	chr2:178588631;178588630;178588629	chr2:179453358;179453357;179453356
N2A	18464	55615;55616;55617	chr2:178588631;178588630;178588629	chr2:179453358;179453357;179453356
N2B	11967	36124;36125;36126	chr2:178588631;178588630;178588629	chr2:179453358;179453357;179453356
Novex-1	12092	36499;36500;36501	chr2:178588631;178588630;178588629	chr2:179453358;179453357;179453356
Novex-2	12159	36700;36701;36702	chr2:178588631;178588630;178588629	chr2:179453358;179453357;179453356
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-40
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1948
• 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
H/R	rs767798579	-1.322	0.999	N	0.414	0.429	0.215109475489	gnomAD-2.1.1	1.27E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.76E-05	0
H/R	rs767798579	-1.322	0.999	N	0.414	0.429	0.215109475489	gnomAD-4.0.0	2.76421E-06	None	None	None	None	N	None	0	0	None	0	2.52678E-05	None	0	0	1.80867E-06	0	1.67409E-05

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
H/A	0.5285	ambiguous	0.4662	ambiguous	-0.69	Destabilizing	0.993	D	0.455	neutral	None	None	None	None	N
H/C	0.1962	likely_benign	0.1763	benign	0.342	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
H/D	0.6289	likely_pathogenic	0.575	pathogenic	-0.823	Destabilizing	0.999	D	0.375	neutral	N	0.503280063	None	None	N
H/E	0.6241	likely_pathogenic	0.5629	ambiguous	-0.702	Destabilizing	0.998	D	0.414	neutral	None	None	None	None	N
H/F	0.4631	ambiguous	0.4203	ambiguous	0.794	Stabilizing	0.991	D	0.366	neutral	None	None	None	None	N
H/G	0.6136	likely_pathogenic	0.5295	ambiguous	-1.08	Destabilizing	0.998	D	0.451	neutral	None	None	None	None	N
H/I	0.5494	ambiguous	0.5078	ambiguous	0.408	Stabilizing	0.998	D	0.594	neutral	None	None	None	None	N
H/K	0.3838	ambiguous	0.3455	ambiguous	-0.353	Destabilizing	0.998	D	0.367	neutral	None	None	None	None	N
H/L	0.2601	likely_benign	0.2387	benign	0.408	Stabilizing	0.98	D	0.537	neutral	N	0.483347508	None	None	N
H/M	0.616	likely_pathogenic	0.5697	pathogenic	0.264	Stabilizing	1.0	D	0.522	neutral	None	None	None	None	N
H/N	0.2153	likely_benign	0.1976	benign	-0.569	Destabilizing	0.997	D	0.457	neutral	N	0.459201212	None	None	N
H/P	0.9385	likely_pathogenic	0.9014	pathogenic	0.061	Stabilizing	0.999	D	0.496	neutral	N	0.488547987	None	None	N
H/Q	0.3146	likely_benign	0.2818	benign	-0.294	Destabilizing	0.999	D	0.421	neutral	N	0.468647414	None	None	N
H/R	0.155	likely_benign	0.1373	benign	-1.031	Destabilizing	0.999	D	0.414	neutral	N	0.450829658	None	None	N
H/S	0.431	ambiguous	0.3726	ambiguous	-0.448	Destabilizing	0.993	D	0.353	neutral	None	None	None	None	N
H/T	0.4885	ambiguous	0.419	ambiguous	-0.221	Destabilizing	0.998	D	0.469	neutral	None	None	None	None	N
H/V	0.4463	ambiguous	0.3986	ambiguous	0.061	Stabilizing	0.996	D	0.557	neutral	None	None	None	None	N
H/W	0.6389	likely_pathogenic	0.5625	ambiguous	1.099	Stabilizing	1.0	D	0.529	neutral	None	None	None	None	N
H/Y	0.1832	likely_benign	0.1589	benign	1.082	Stabilizing	0.4	N	0.271	neutral	N	0.465924281	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.