TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31987	96184;96185;96186	chr2:178544270;178544269;178544268	chr2:179408997;179408996;179408995
N2AB	30346	91261;91262;91263	chr2:178544270;178544269;178544268	chr2:179408997;179408996;179408995
N2A	29419	88480;88481;88482	chr2:178544270;178544269;178544268	chr2:179408997;179408996;179408995
N2B	22922	68989;68990;68991	chr2:178544270;178544269;178544268	chr2:179408997;179408996;179408995
Novex-1	23047	69364;69365;69366	chr2:178544270;178544269;178544268	chr2:179408997;179408996;179408995
Novex-2	23114	69565;69566;69567	chr2:178544270;178544269;178544268	chr2:179408997;179408996;179408995
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: Fn3-121
• Domain position: 79
• Structural Position: 110
• Q(SASA): 0.072
• 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
A/S	None	None	0.568	D	0.373	0.468	0.484837542351	gnomAD-4.0.0	6.84223E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99504E-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	0.8007	likely_pathogenic	0.8136	pathogenic	-1.766	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
A/D	0.9959	likely_pathogenic	0.9963	pathogenic	-3.029	Highly Destabilizing	0.993	D	0.805	deleterious	D	0.640131085	None	None	N
A/E	0.9946	likely_pathogenic	0.995	pathogenic	-2.812	Highly Destabilizing	0.995	D	0.802	deleterious	None	None	None	None	N
A/F	0.9909	likely_pathogenic	0.9922	pathogenic	-0.708	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
A/G	0.3731	ambiguous	0.3923	ambiguous	-2.007	Highly Destabilizing	0.955	D	0.635	neutral	D	0.590226403	None	None	N
A/H	0.9967	likely_pathogenic	0.9972	pathogenic	-2.091	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
A/I	0.9531	likely_pathogenic	0.9666	pathogenic	-0.327	Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	N
A/K	0.9989	likely_pathogenic	0.9991	pathogenic	-1.462	Destabilizing	0.995	D	0.802	deleterious	None	None	None	None	N
A/L	0.9321	likely_pathogenic	0.9387	pathogenic	-0.327	Destabilizing	0.983	D	0.775	deleterious	None	None	None	None	N
A/M	0.9492	likely_pathogenic	0.9568	pathogenic	-0.846	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/N	0.9885	likely_pathogenic	0.9905	pathogenic	-1.912	Destabilizing	0.995	D	0.803	deleterious	None	None	None	None	N
A/P	0.9784	likely_pathogenic	0.9714	pathogenic	-0.702	Destabilizing	0.997	D	0.813	deleterious	D	0.61398756	None	None	N
A/Q	0.9903	likely_pathogenic	0.9916	pathogenic	-1.678	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
A/R	0.9956	likely_pathogenic	0.9963	pathogenic	-1.511	Destabilizing	0.995	D	0.819	deleterious	None	None	None	None	N
A/S	0.2262	likely_benign	0.248	benign	-2.259	Highly Destabilizing	0.568	D	0.373	neutral	D	0.550617329	None	None	N
A/T	0.6218	likely_pathogenic	0.6893	pathogenic	-1.932	Destabilizing	0.955	D	0.667	neutral	D	0.597564591	None	None	N
A/V	0.749	likely_pathogenic	0.8087	pathogenic	-0.702	Destabilizing	0.977	D	0.731	prob.delet.	D	0.590458568	None	None	N
A/W	0.9991	likely_pathogenic	0.9992	pathogenic	-1.43	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
A/Y	0.9966	likely_pathogenic	0.9969	pathogenic	-1.036	Destabilizing	1.0	D	0.85	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.