TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31264	94015;94016;94017	chr2:178547836;178547835;178547834	chr2:179412563;179412562;179412561
N2AB	29623	89092;89093;89094	chr2:178547836;178547835;178547834	chr2:179412563;179412562;179412561
N2A	28696	86311;86312;86313	chr2:178547836;178547835;178547834	chr2:179412563;179412562;179412561
N2B	22199	66820;66821;66822	chr2:178547836;178547835;178547834	chr2:179412563;179412562;179412561
Novex-1	22324	67195;67196;67197	chr2:178547836;178547835;178547834	chr2:179412563;179412562;179412561
Novex-2	22391	67396;67397;67398	chr2:178547836;178547835;178547834	chr2:179412563;179412562;179412561
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-151
• Domain position: 47
• Structural Position: 123
• Q(SASA): 0.2931
• 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/T	rs773835374	-1.843	1.0	N	0.706	0.59	0.793015639883	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/T	rs773835374	-1.843	1.0	N	0.706	0.59	0.793015639883	gnomAD-4.0.0	3.18218E-06	None	None	None	None	N	None	0	2.28676E-05	None	0	0	None	0	0	2.85783E-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
I/A	0.6197	likely_pathogenic	0.694	pathogenic	-2.049	Highly Destabilizing	0.999	D	0.502	neutral	None	None	None	None	N
I/C	0.7241	likely_pathogenic	0.7767	pathogenic	-1.664	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
I/D	0.959	likely_pathogenic	0.9697	pathogenic	-1.209	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
I/E	0.8831	likely_pathogenic	0.9079	pathogenic	-1.145	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
I/F	0.2052	likely_benign	0.2041	benign	-1.502	Destabilizing	1.0	D	0.695	prob.neutral	N	0.490318047	None	None	N
I/G	0.8861	likely_pathogenic	0.917	pathogenic	-2.442	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
I/H	0.7849	likely_pathogenic	0.8191	pathogenic	-1.652	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
I/K	0.735	likely_pathogenic	0.7677	pathogenic	-1.324	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
I/L	0.1557	likely_benign	0.1751	benign	-1.005	Destabilizing	0.993	D	0.327	neutral	N	0.520148962	None	None	N
I/M	0.1425	likely_benign	0.1504	benign	-0.951	Destabilizing	1.0	D	0.709	prob.delet.	N	0.487493663	None	None	N
I/N	0.7208	likely_pathogenic	0.7629	pathogenic	-1.245	Destabilizing	1.0	D	0.814	deleterious	N	0.514969668	None	None	N
I/P	0.9582	likely_pathogenic	0.9679	pathogenic	-1.325	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
I/Q	0.7627	likely_pathogenic	0.8059	pathogenic	-1.342	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
I/R	0.647	likely_pathogenic	0.6829	pathogenic	-0.844	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
I/S	0.6552	likely_pathogenic	0.7143	pathogenic	-2.033	Highly Destabilizing	1.0	D	0.748	deleterious	N	0.499067459	None	None	N
I/T	0.5783	likely_pathogenic	0.6245	pathogenic	-1.827	Destabilizing	1.0	D	0.706	prob.neutral	N	0.519362315	None	None	N
I/V	0.0845	likely_benign	0.0925	benign	-1.325	Destabilizing	0.993	D	0.315	neutral	N	0.475816608	None	None	N
I/W	0.8076	likely_pathogenic	0.8296	pathogenic	-1.55	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
I/Y	0.63	likely_pathogenic	0.6468	pathogenic	-1.319	Destabilizing	1.0	D	0.768	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.