TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26728	80407;80408;80409	chr2:178565950;178565949;178565948	chr2:179430677;179430676;179430675
N2AB	25087	75484;75485;75486	chr2:178565950;178565949;178565948	chr2:179430677;179430676;179430675
N2A	24160	72703;72704;72705	chr2:178565950;178565949;178565948	chr2:179430677;179430676;179430675
N2B	17663	53212;53213;53214	chr2:178565950;178565949;178565948	chr2:179430677;179430676;179430675
Novex-1	17788	53587;53588;53589	chr2:178565950;178565949;178565948	chr2:179430677;179430676;179430675
Novex-2	17855	53788;53789;53790	chr2:178565950;178565949;178565948	chr2:179430677;179430676;179430675
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-82
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9436
• 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
K/E	None	None	0.978	N	0.578	0.26	0.30212335484	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-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
K/A	0.9425	likely_pathogenic	0.9531	pathogenic	-0.088	Destabilizing	0.997	D	0.584	neutral	None	None	None	None	N
K/C	0.9785	likely_pathogenic	0.981	pathogenic	-0.616	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/D	0.9891	likely_pathogenic	0.9919	pathogenic	-0.451	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	N
K/E	0.9427	likely_pathogenic	0.9613	pathogenic	-0.474	Destabilizing	0.978	D	0.578	neutral	N	0.508915169	None	None	N
K/F	0.9863	likely_pathogenic	0.9862	pathogenic	-0.478	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
K/G	0.9562	likely_pathogenic	0.9635	pathogenic	-0.179	Destabilizing	1.0	D	0.546	neutral	None	None	None	None	N
K/H	0.8556	likely_pathogenic	0.8734	pathogenic	-0.22	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
K/I	0.9217	likely_pathogenic	0.939	pathogenic	0.07	Stabilizing	0.995	D	0.679	prob.neutral	N	0.484219574	None	None	N
K/L	0.8392	likely_pathogenic	0.874	pathogenic	0.07	Stabilizing	0.976	D	0.546	neutral	None	None	None	None	N
K/M	0.7558	likely_pathogenic	0.8077	pathogenic	-0.262	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
K/N	0.9734	likely_pathogenic	0.9805	pathogenic	-0.171	Destabilizing	1.0	D	0.619	neutral	N	0.511302113	None	None	N
K/P	0.9653	likely_pathogenic	0.9676	pathogenic	0.037	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/Q	0.6782	likely_pathogenic	0.7479	pathogenic	-0.312	Destabilizing	0.766	D	0.487	neutral	N	0.465061681	None	None	N
K/R	0.1425	likely_benign	0.1351	benign	-0.243	Destabilizing	0.982	D	0.555	neutral	N	0.487350605	None	None	N
K/S	0.9756	likely_pathogenic	0.9802	pathogenic	-0.507	Destabilizing	0.997	D	0.588	neutral	None	None	None	None	N
K/T	0.8904	likely_pathogenic	0.9205	pathogenic	-0.432	Destabilizing	0.998	D	0.597	neutral	N	0.46664507	None	None	N
K/V	0.8999	likely_pathogenic	0.9209	pathogenic	0.037	Stabilizing	0.991	D	0.616	neutral	None	None	None	None	N
K/W	0.9773	likely_pathogenic	0.9769	pathogenic	-0.593	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/Y	0.9613	likely_pathogenic	0.9632	pathogenic	-0.259	Destabilizing	0.998	D	0.639	neutral	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.