TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35306	106141;106142;106143	chr2:178530699;178530698;178530697	chr2:179395426;179395425;179395424
N2AB	33665	101218;101219;101220	chr2:178530699;178530698;178530697	chr2:179395426;179395425;179395424
N2A	32738	98437;98438;98439	chr2:178530699;178530698;178530697	chr2:179395426;179395425;179395424
N2B	26241	78946;78947;78948	chr2:178530699;178530698;178530697	chr2:179395426;179395425;179395424
Novex-1	26366	79321;79322;79323	chr2:178530699;178530698;178530697	chr2:179395426;179395425;179395424
Novex-2	26433	79522;79523;79524	chr2:178530699;178530698;178530697	chr2:179395426;179395425;179395424
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-165
• Domain position: 21
• Structural Position: 34
• Q(SASA): 0.1509
• 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
V/M	rs1434315858	None	0.074	N	0.535	0.075	0.523546030903	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
V/M	rs1434315858	None	0.074	N	0.535	0.075	0.523546030903	gnomAD-4.0.0	1.97135E-05	None	None	None	None	N	None	7.23973E-05	0	None	0	0	None	0	0	0	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
V/A	0.052	likely_benign	0.0706	benign	-1.368	Destabilizing	None	N	0.219	neutral	N	0.433855342	None	None	N
V/C	0.4881	ambiguous	0.6036	pathogenic	-1.245	Destabilizing	0.177	N	0.541	neutral	None	None	None	None	N
V/D	0.1519	likely_benign	0.2061	benign	-1.282	Destabilizing	0.029	N	0.595	neutral	None	None	None	None	N
V/E	0.1218	likely_benign	0.1379	benign	-1.3	Destabilizing	0.022	N	0.509	neutral	N	0.429486885	None	None	N
V/F	0.1166	likely_benign	0.1406	benign	-1.271	Destabilizing	0.096	N	0.569	neutral	None	None	None	None	N
V/G	0.1073	likely_benign	0.1332	benign	-1.634	Destabilizing	0.005	N	0.51	neutral	N	0.502139204	None	None	N
V/H	0.2922	likely_benign	0.3359	benign	-1.129	Destabilizing	0.712	D	0.581	neutral	None	None	None	None	N
V/I	0.0754	likely_benign	0.084	benign	-0.747	Destabilizing	None	N	0.207	neutral	None	None	None	None	N
V/K	0.1431	likely_benign	0.1348	benign	-0.928	Destabilizing	0.029	N	0.514	neutral	None	None	None	None	N
V/L	0.1202	likely_benign	0.1447	benign	-0.747	Destabilizing	None	N	0.248	neutral	N	0.466045118	None	None	N
V/M	0.0888	likely_benign	0.0862	benign	-0.72	Destabilizing	0.074	N	0.535	neutral	N	0.494674514	None	None	N
V/N	0.1136	likely_benign	0.146	benign	-0.807	Destabilizing	0.096	N	0.61	neutral	None	None	None	None	N
V/P	0.4165	ambiguous	0.5119	ambiguous	-0.92	Destabilizing	0.096	N	0.568	neutral	None	None	None	None	N
V/Q	0.1462	likely_benign	0.1481	benign	-1.046	Destabilizing	0.177	N	0.556	neutral	None	None	None	None	N
V/R	0.1192	likely_benign	0.112	benign	-0.456	Destabilizing	0.096	N	0.612	neutral	None	None	None	None	N
V/S	0.0691	likely_benign	0.0968	benign	-1.34	Destabilizing	None	N	0.422	neutral	None	None	None	None	N
V/T	0.0678	likely_benign	0.0837	benign	-1.252	Destabilizing	0.006	N	0.409	neutral	None	None	None	None	N
V/W	0.61	likely_pathogenic	0.6691	pathogenic	-1.379	Destabilizing	0.712	D	0.621	neutral	None	None	None	None	N
V/Y	0.3496	ambiguous	0.4102	ambiguous	-1.048	Destabilizing	0.177	N	0.563	neutral	None	None	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.