TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20259	61000;61001;61002	chr2:178590950;178590949;178590948	chr2:179455677;179455676;179455675
N2AB	18618	56077;56078;56079	chr2:178590950;178590949;178590948	chr2:179455677;179455676;179455675
N2A	17691	53296;53297;53298	chr2:178590950;178590949;178590948	chr2:179455677;179455676;179455675
N2B	11194	33805;33806;33807	chr2:178590950;178590949;178590948	chr2:179455677;179455676;179455675
Novex-1	11319	34180;34181;34182	chr2:178590950;178590949;178590948	chr2:179455677;179455676;179455675
Novex-2	11386	34381;34382;34383	chr2:178590950;178590949;178590948	chr2:179455677;179455676;179455675
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: Fn3-34
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.7666
• 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	None	None	0.958	N	0.669	0.247	0.302793454619	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8601E-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	0.1374	likely_benign	0.1566	benign	-0.308	Destabilizing	0.919	D	0.669	prob.neutral	N	0.449611441	None	None	N
D/C	0.498	ambiguous	0.5237	ambiguous	-0.132	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
D/E	0.1268	likely_benign	0.1357	benign	-0.508	Destabilizing	0.06	N	0.196	neutral	N	0.332090837	None	None	N
D/F	0.419	ambiguous	0.4673	ambiguous	0.407	Stabilizing	0.991	D	0.81	deleterious	None	None	None	None	N
D/G	0.2153	likely_benign	0.2816	benign	-0.695	Destabilizing	0.958	D	0.682	prob.neutral	N	0.462426023	None	None	N
D/H	0.2215	likely_benign	0.2627	benign	0.251	Stabilizing	0.999	D	0.705	prob.delet.	N	0.496365238	None	None	N
D/I	0.1606	likely_benign	0.1642	benign	0.725	Stabilizing	0.319	N	0.522	neutral	None	None	None	None	N
D/K	0.2614	likely_benign	0.3168	benign	-0.113	Destabilizing	0.938	D	0.701	prob.delet.	None	None	None	None	N
D/L	0.1796	likely_benign	0.1964	benign	0.725	Stabilizing	0.883	D	0.657	prob.neutral	None	None	None	None	N
D/M	0.4178	ambiguous	0.4288	ambiguous	1.018	Stabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
D/N	0.1019	likely_benign	0.104	benign	-0.8	Destabilizing	0.958	D	0.669	prob.neutral	N	0.477163402	None	None	N
D/P	0.4764	ambiguous	0.5776	pathogenic	0.407	Stabilizing	0.997	D	0.71	prob.delet.	None	None	None	None	N
D/Q	0.2484	likely_benign	0.2811	benign	-0.602	Destabilizing	0.981	D	0.61	neutral	None	None	None	None	N
D/R	0.3292	likely_benign	0.3952	ambiguous	0.142	Stabilizing	0.981	D	0.777	deleterious	None	None	None	None	N
D/S	0.1214	likely_benign	0.1266	benign	-1.025	Destabilizing	0.938	D	0.527	neutral	None	None	None	None	N
D/T	0.152	likely_benign	0.1533	benign	-0.69	Destabilizing	0.968	D	0.703	prob.delet.	None	None	None	None	N
D/V	0.0986	likely_benign	0.1018	benign	0.407	Stabilizing	0.851	D	0.665	prob.neutral	N	0.452478388	None	None	N
D/W	0.8235	likely_pathogenic	0.8535	pathogenic	0.646	Stabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
D/Y	0.1584	likely_benign	0.1877	benign	0.688	Stabilizing	0.996	D	0.819	deleterious	N	0.504080644	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.