TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25124	75595;75596;75597	chr2:178570762;178570761;178570760	chr2:179435489;179435488;179435487
N2AB	23483	70672;70673;70674	chr2:178570762;178570761;178570760	chr2:179435489;179435488;179435487
N2A	22556	67891;67892;67893	chr2:178570762;178570761;178570760	chr2:179435489;179435488;179435487
N2B	16059	48400;48401;48402	chr2:178570762;178570761;178570760	chr2:179435489;179435488;179435487
Novex-1	16184	48775;48776;48777	chr2:178570762;178570761;178570760	chr2:179435489;179435488;179435487
Novex-2	16251	48976;48977;48978	chr2:178570762;178570761;178570760	chr2:179435489;179435488;179435487
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: Ig-134
• Domain position: 14
• Structural Position: 18
• Q(SASA): 0.6234
• Predicted PPI site: I

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/P	None	None	0.106	N	0.525	0.285	0.380052290102	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
H/A	0.2309	likely_benign	0.2563	benign	0.083	Stabilizing	0.016	N	0.443	neutral	None	None	None	None	I
H/C	0.1413	likely_benign	0.1732	benign	0.539	Stabilizing	0.864	D	0.469	neutral	None	None	None	None	I
H/D	0.2669	likely_benign	0.2987	benign	-0.203	Destabilizing	0.012	N	0.452	neutral	N	0.462388738	None	None	I
H/E	0.3057	likely_benign	0.3605	ambiguous	-0.162	Destabilizing	0.016	N	0.245	neutral	None	None	None	None	I
H/F	0.2609	likely_benign	0.31	benign	0.927	Stabilizing	0.628	D	0.462	neutral	None	None	None	None	I
H/G	0.291	likely_benign	0.3269	benign	-0.216	Destabilizing	0.016	N	0.452	neutral	None	None	None	None	I
H/I	0.2968	likely_benign	0.3323	benign	0.86	Stabilizing	0.356	N	0.516	neutral	None	None	None	None	I
H/K	0.175	likely_benign	0.1925	benign	-0.014	Destabilizing	0.016	N	0.413	neutral	None	None	None	None	I
H/L	0.0956	likely_benign	0.102	benign	0.86	Stabilizing	0.055	N	0.483	neutral	N	0.424947857	None	None	I
H/M	0.3546	ambiguous	0.389	ambiguous	0.594	Stabilizing	0.356	N	0.487	neutral	None	None	None	None	I
H/N	0.0863	likely_benign	0.0873	benign	-0.096	Destabilizing	None	N	0.159	neutral	N	0.395510385	None	None	I
H/P	0.1449	likely_benign	0.1488	benign	0.626	Stabilizing	0.106	N	0.525	neutral	N	0.442880257	None	None	I
H/Q	0.1536	likely_benign	0.1686	benign	0.048	Stabilizing	None	N	0.217	neutral	N	0.414306789	None	None	I
H/R	0.0851	likely_benign	0.0953	benign	-0.612	Destabilizing	None	N	0.174	neutral	N	0.390584567	None	None	I
H/S	0.198	likely_benign	0.2154	benign	0.021	Stabilizing	0.001	N	0.206	neutral	None	None	None	None	I
H/T	0.2364	likely_benign	0.2726	benign	0.163	Stabilizing	0.016	N	0.499	neutral	None	None	None	None	I
H/V	0.2218	likely_benign	0.2497	benign	0.626	Stabilizing	0.072	N	0.494	neutral	None	None	None	None	I
H/W	0.3807	ambiguous	0.4485	ambiguous	0.982	Stabilizing	0.864	D	0.484	neutral	None	None	None	None	I
H/Y	0.0914	likely_benign	0.1057	benign	1.181	Stabilizing	0.106	N	0.343	neutral	N	0.470162859	None	None	I

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.