TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31698	95317;95318;95319	chr2:178546239;178546238;178546237	chr2:179410966;179410965;179410964
N2AB	30057	90394;90395;90396	chr2:178546239;178546238;178546237	chr2:179410966;179410965;179410964
N2A	29130	87613;87614;87615	chr2:178546239;178546238;178546237	chr2:179410966;179410965;179410964
N2B	22633	68122;68123;68124	chr2:178546239;178546238;178546237	chr2:179410966;179410965;179410964
Novex-1	22758	68497;68498;68499	chr2:178546239;178546238;178546237	chr2:179410966;179410965;179410964
Novex-2	22825	68698;68699;68700	chr2:178546239;178546238;178546237	chr2:179410966;179410965;179410964
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-152
• Domain position: 78
• Structural Position: 168
• Q(SASA): 0.3541
• 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
A/P	None	None	0.117	N	0.556	0.124	0.353974658523	gnomAD-4.0.0	1.5943E-06	None	None	None	None	I	None	0	0	None	0	2.77316E-05	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
A/C	0.3288	likely_benign	0.3457	ambiguous	-0.822	Destabilizing	0.824	D	0.481	neutral	None	None	None	None	I
A/D	0.2153	likely_benign	0.2065	benign	-0.621	Destabilizing	0.062	N	0.565	neutral	N	0.478878343	None	None	I
A/E	0.1715	likely_benign	0.1851	benign	-0.763	Destabilizing	0.035	N	0.493	neutral	None	None	None	None	I
A/F	0.2741	likely_benign	0.2736	benign	-0.869	Destabilizing	0.555	D	0.601	neutral	None	None	None	None	I
A/G	0.1419	likely_benign	0.1418	benign	-0.418	Destabilizing	0.027	N	0.411	neutral	N	0.485883821	None	None	I
A/H	0.3258	likely_benign	0.3469	ambiguous	-0.484	Destabilizing	0.555	D	0.567	neutral	None	None	None	None	I
A/I	0.1622	likely_benign	0.164	benign	-0.334	Destabilizing	0.081	N	0.559	neutral	None	None	None	None	I
A/K	0.3448	ambiguous	0.369	ambiguous	-0.816	Destabilizing	0.081	N	0.507	neutral	None	None	None	None	I
A/L	0.1298	likely_benign	0.1358	benign	-0.334	Destabilizing	0.035	N	0.487	neutral	None	None	None	None	I
A/M	0.1236	likely_benign	0.1285	benign	-0.432	Destabilizing	0.555	D	0.541	neutral	None	None	None	None	I
A/N	0.1646	likely_benign	0.166	benign	-0.496	Destabilizing	0.081	N	0.551	neutral	None	None	None	None	I
A/P	0.4228	ambiguous	0.4105	ambiguous	-0.302	Destabilizing	0.117	N	0.556	neutral	N	0.50435279	None	None	I
A/Q	0.2147	likely_benign	0.2392	benign	-0.763	Destabilizing	0.002	N	0.266	neutral	None	None	None	None	I
A/R	0.3281	likely_benign	0.3511	ambiguous	-0.343	Destabilizing	0.081	N	0.55	neutral	None	None	None	None	I
A/S	0.0782	likely_benign	0.0768	benign	-0.683	Destabilizing	None	N	0.1	neutral	N	0.368323783	None	None	I
A/T	0.0652	likely_benign	0.0653	benign	-0.745	Destabilizing	None	N	0.087	neutral	N	0.390467137	None	None	I
A/V	0.0931	likely_benign	0.0919	benign	-0.302	Destabilizing	0.027	N	0.425	neutral	N	0.472395087	None	None	I
A/W	0.6181	likely_pathogenic	0.6151	pathogenic	-1.036	Destabilizing	0.935	D	0.617	neutral	None	None	None	None	I
A/Y	0.3532	ambiguous	0.3501	ambiguous	-0.691	Destabilizing	0.555	D	0.6	neutral	None	None	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.