TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35630	107113;107114;107115	chr2:178528863;178528862;178528861	chr2:179393590;179393589;179393588
N2AB	33989	102190;102191;102192	chr2:178528863;178528862;178528861	chr2:179393590;179393589;179393588
N2A	33062	99409;99410;99411	chr2:178528863;178528862;178528861	chr2:179393590;179393589;179393588
N2B	26565	79918;79919;79920	chr2:178528863;178528862;178528861	chr2:179393590;179393589;179393588
Novex-1	26690	80293;80294;80295	chr2:178528863;178528862;178528861	chr2:179393590;179393589;179393588
Novex-2	26757	80494;80495;80496	chr2:178528863;178528862;178528861	chr2:179393590;179393589;179393588
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-167
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.2302
• 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
I/V	rs754830278	-0.804	0.19	N	0.498	0.094	0.314716216878	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs754830278	-0.804	0.19	N	0.498	0.094	0.314716216878	gnomAD-4.0.0	1.5909E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
I/A	0.6356	likely_pathogenic	0.63	pathogenic	-1.413	Destabilizing	0.775	D	0.673	neutral	None	None	None	None	N
I/C	0.9516	likely_pathogenic	0.9488	pathogenic	-1.069	Destabilizing	0.996	D	0.738	prob.delet.	None	None	None	None	N
I/D	0.9659	likely_pathogenic	0.9697	pathogenic	-1.379	Destabilizing	0.987	D	0.819	deleterious	None	None	None	None	N
I/E	0.9322	likely_pathogenic	0.9413	pathogenic	-1.433	Destabilizing	0.961	D	0.815	deleterious	None	None	None	None	N
I/F	0.3102	likely_benign	0.3377	benign	-1.443	Destabilizing	0.82	D	0.701	prob.neutral	N	0.487695401	None	None	N
I/G	0.9336	likely_pathogenic	0.9345	pathogenic	-1.65	Destabilizing	0.961	D	0.803	deleterious	None	None	None	None	N
I/H	0.898	likely_pathogenic	0.9114	pathogenic	-0.955	Destabilizing	0.996	D	0.822	deleterious	None	None	None	None	N
I/K	0.8315	likely_pathogenic	0.8596	pathogenic	-0.787	Destabilizing	0.923	D	0.802	deleterious	None	None	None	None	N
I/L	0.2492	likely_benign	0.2444	benign	-0.86	Destabilizing	0.003	N	0.285	neutral	N	0.486828609	None	None	N
I/M	0.2062	likely_benign	0.2039	benign	-0.603	Destabilizing	0.19	N	0.524	neutral	N	0.487868759	None	None	N
I/N	0.7473	likely_pathogenic	0.7583	pathogenic	-0.652	Destabilizing	0.949	D	0.821	deleterious	N	0.488215476	None	None	N
I/P	0.9476	likely_pathogenic	0.9582	pathogenic	-1.014	Destabilizing	0.987	D	0.82	deleterious	None	None	None	None	N
I/Q	0.8911	likely_pathogenic	0.8987	pathogenic	-0.973	Destabilizing	0.961	D	0.819	deleterious	None	None	None	None	N
I/R	0.7788	likely_pathogenic	0.813	pathogenic	-0.175	Destabilizing	0.923	D	0.819	deleterious	None	None	None	None	N
I/S	0.7037	likely_pathogenic	0.7127	pathogenic	-1.161	Destabilizing	0.901	D	0.787	deleterious	N	0.488042117	None	None	N
I/T	0.4622	ambiguous	0.4829	ambiguous	-1.109	Destabilizing	0.722	D	0.763	deleterious	N	0.487001967	None	None	N
I/V	0.132	likely_benign	0.1292	benign	-1.014	Destabilizing	0.19	N	0.498	neutral	N	0.476080393	None	None	N
I/W	0.9542	likely_pathogenic	0.9585	pathogenic	-1.464	Destabilizing	0.996	D	0.826	deleterious	None	None	None	None	N
I/Y	0.8216	likely_pathogenic	0.8451	pathogenic	-1.161	Destabilizing	0.961	D	0.774	deleterious	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.