TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25184	75775;75776;75777	chr2:178570582;178570581;178570580	chr2:179435309;179435308;179435307
N2AB	23543	70852;70853;70854	chr2:178570582;178570581;178570580	chr2:179435309;179435308;179435307
N2A	22616	68071;68072;68073	chr2:178570582;178570581;178570580	chr2:179435309;179435308;179435307
N2B	16119	48580;48581;48582	chr2:178570582;178570581;178570580	chr2:179435309;179435308;179435307
Novex-1	16244	48955;48956;48957	chr2:178570582;178570581;178570580	chr2:179435309;179435308;179435307
Novex-2	16311	49156;49157;49158	chr2:178570582;178570581;178570580	chr2:179435309;179435308;179435307
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-134
• Domain position: 74
• Structural Position: 156
• Q(SASA): 0.0423
• 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
L/V	None	None	0.618	N	0.708	0.103	0.128392430309	gnomAD-4.0.0	6.84375E-07	None	None	None	None	N	None	0	0	None	0	2.52678E-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
L/A	0.9054	likely_pathogenic	0.9347	pathogenic	-2.654	Highly Destabilizing	0.968	D	0.754	deleterious	None	None	None	None	N
L/C	0.7861	likely_pathogenic	0.8468	pathogenic	-1.786	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9997	pathogenic	-3.196	Highly Destabilizing	0.998	D	0.901	deleterious	None	None	None	None	N
L/E	0.9951	likely_pathogenic	0.9968	pathogenic	-2.942	Highly Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
L/F	0.6142	likely_pathogenic	0.677	pathogenic	-1.644	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	N
L/G	0.9858	likely_pathogenic	0.9912	pathogenic	-3.219	Highly Destabilizing	0.995	D	0.879	deleterious	None	None	None	None	N
L/H	0.9854	likely_pathogenic	0.9909	pathogenic	-2.696	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/I	0.096	likely_benign	0.102	benign	-0.998	Destabilizing	0.086	N	0.412	neutral	None	None	None	None	N
L/K	0.9899	likely_pathogenic	0.9938	pathogenic	-2.112	Highly Destabilizing	0.995	D	0.887	deleterious	None	None	None	None	N
L/M	0.295	likely_benign	0.3321	benign	-0.83	Destabilizing	0.988	D	0.747	deleterious	N	0.475152722	None	None	N
L/N	0.9956	likely_pathogenic	0.997	pathogenic	-2.562	Highly Destabilizing	0.998	D	0.91	deleterious	None	None	None	None	N
L/P	0.9919	likely_pathogenic	0.9948	pathogenic	-1.534	Destabilizing	0.998	D	0.909	deleterious	N	0.505284846	None	None	N
L/Q	0.9725	likely_pathogenic	0.982	pathogenic	-2.389	Highly Destabilizing	0.999	D	0.913	deleterious	N	0.505284846	None	None	N
L/R	0.9781	likely_pathogenic	0.9859	pathogenic	-1.862	Destabilizing	0.998	D	0.906	deleterious	N	0.505284846	None	None	N
L/S	0.9873	likely_pathogenic	0.9919	pathogenic	-3.211	Highly Destabilizing	0.995	D	0.889	deleterious	None	None	None	None	N
L/T	0.9479	likely_pathogenic	0.9633	pathogenic	-2.806	Highly Destabilizing	0.991	D	0.817	deleterious	None	None	None	None	N
L/V	0.118	likely_benign	0.1294	benign	-1.534	Destabilizing	0.618	D	0.708	prob.delet.	N	0.501498046	None	None	N
L/W	0.9465	likely_pathogenic	0.9667	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/Y	0.9627	likely_pathogenic	0.9766	pathogenic	-1.78	Destabilizing	0.995	D	0.84	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.