TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20351	61276;61277;61278	chr2:178590674;178590673;178590672	chr2:179455401;179455400;179455399
N2AB	18710	56353;56354;56355	chr2:178590674;178590673;178590672	chr2:179455401;179455400;179455399
N2A	17783	53572;53573;53574	chr2:178590674;178590673;178590672	chr2:179455401;179455400;179455399
N2B	11286	34081;34082;34083	chr2:178590674;178590673;178590672	chr2:179455401;179455400;179455399
Novex-1	11411	34456;34457;34458	chr2:178590674;178590673;178590672	chr2:179455401;179455400;179455399
Novex-2	11478	34657;34658;34659	chr2:178590674;178590673;178590672	chr2:179455401;179455400;179455399
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-35
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.5574
• 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/G	None	None	0.989	N	0.592	0.333	0.33110744837	gnomAD-4.0.0	1.36892E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79943E-06	0	0
A/T	None	None	0.977	N	0.628	0.399	0.357724736475	gnomAD-4.0.0	3.1851E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72135E-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
A/C	0.6168	likely_pathogenic	0.6391	pathogenic	-0.868	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
A/D	0.9236	likely_pathogenic	0.9414	pathogenic	-0.471	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
A/E	0.8671	likely_pathogenic	0.8817	pathogenic	-0.624	Destabilizing	0.997	D	0.713	prob.delet.	N	0.486257036	None	None	I
A/F	0.7385	likely_pathogenic	0.748	pathogenic	-0.904	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	I
A/G	0.3907	ambiguous	0.4129	ambiguous	-0.34	Destabilizing	0.989	D	0.592	neutral	N	0.482711863	None	None	I
A/H	0.9027	likely_pathogenic	0.9171	pathogenic	-0.238	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
A/I	0.4878	ambiguous	0.5196	ambiguous	-0.427	Destabilizing	0.966	D	0.608	neutral	None	None	None	None	I
A/K	0.9528	likely_pathogenic	0.9548	pathogenic	-0.618	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	I
A/L	0.5133	ambiguous	0.5741	pathogenic	-0.427	Destabilizing	0.966	D	0.495	neutral	None	None	None	None	I
A/M	0.6093	likely_pathogenic	0.611	pathogenic	-0.533	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	I
A/N	0.864	likely_pathogenic	0.8712	pathogenic	-0.346	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
A/P	0.9006	likely_pathogenic	0.9292	pathogenic	-0.358	Destabilizing	0.999	D	0.717	prob.delet.	D	0.532495632	None	None	I
A/Q	0.8549	likely_pathogenic	0.8508	pathogenic	-0.625	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
A/R	0.8802	likely_pathogenic	0.8847	pathogenic	-0.121	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	I
A/S	0.232	likely_benign	0.2091	benign	-0.556	Destabilizing	0.989	D	0.589	neutral	N	0.479802255	None	None	I
A/T	0.4427	ambiguous	0.4007	ambiguous	-0.63	Destabilizing	0.977	D	0.628	neutral	N	0.495273164	None	None	I
A/V	0.2322	likely_benign	0.2124	benign	-0.358	Destabilizing	0.117	N	0.33	neutral	N	0.474074664	None	None	I
A/W	0.9533	likely_pathogenic	0.9633	pathogenic	-1.001	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
A/Y	0.8642	likely_pathogenic	0.8788	pathogenic	-0.681	Destabilizing	0.998	D	0.814	deleterious	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.