TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32459	97600;97601;97602	chr2:178542381;178542380;178542379	chr2:179407108;179407107;179407106
N2AB	30818	92677;92678;92679	chr2:178542381;178542380;178542379	chr2:179407108;179407107;179407106
N2A	29891	89896;89897;89898	chr2:178542381;178542380;178542379	chr2:179407108;179407107;179407106
N2B	23394	70405;70406;70407	chr2:178542381;178542380;178542379	chr2:179407108;179407107;179407106
Novex-1	23519	70780;70781;70782	chr2:178542381;178542380;178542379	chr2:179407108;179407107;179407106
Novex-2	23586	70981;70982;70983	chr2:178542381;178542380;178542379	chr2:179407108;179407107;179407106
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-124
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.1336
• 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
F/I	rs56009327	None	0.982	N	0.442	0.467	0.443285836454	gnomAD-4.0.0	1.8475E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.42869E-05	0	0
F/V	None	None	0.939	N	0.482	0.386	0.550885202691	gnomAD-4.0.0	6.84258E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99514E-07	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
F/A	0.9358	likely_pathogenic	0.9047	pathogenic	-1.628	Destabilizing	0.953	D	0.519	neutral	None	None	None	None	N
F/C	0.5206	ambiguous	0.4411	ambiguous	-1.008	Destabilizing	0.999	D	0.646	neutral	N	0.494239292	None	None	N
F/D	0.9949	likely_pathogenic	0.9927	pathogenic	-1.936	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
F/E	0.9908	likely_pathogenic	0.988	pathogenic	-1.712	Destabilizing	0.993	D	0.686	prob.neutral	None	None	None	None	N
F/G	0.9777	likely_pathogenic	0.9621	pathogenic	-2.06	Highly Destabilizing	0.993	D	0.641	neutral	None	None	None	None	N
F/H	0.8836	likely_pathogenic	0.8683	pathogenic	-0.908	Destabilizing	0.986	D	0.597	neutral	None	None	None	None	N
F/I	0.6227	likely_pathogenic	0.6083	pathogenic	-0.253	Destabilizing	0.982	D	0.442	neutral	N	0.461222797	None	None	N
F/K	0.9868	likely_pathogenic	0.9831	pathogenic	-1.409	Destabilizing	0.993	D	0.691	prob.neutral	None	None	None	None	N
F/L	0.9609	likely_pathogenic	0.948	pathogenic	-0.253	Destabilizing	0.885	D	0.508	neutral	N	0.438017863	None	None	N
F/M	0.7794	likely_pathogenic	0.7479	pathogenic	-0.144	Destabilizing	0.999	D	0.476	neutral	None	None	None	None	N
F/N	0.9693	likely_pathogenic	0.9622	pathogenic	-2.003	Highly Destabilizing	0.993	D	0.727	prob.delet.	None	None	None	None	N
F/P	0.9993	likely_pathogenic	0.9989	pathogenic	-0.717	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
F/Q	0.9672	likely_pathogenic	0.9587	pathogenic	-1.766	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	N
F/R	0.9691	likely_pathogenic	0.9581	pathogenic	-1.349	Destabilizing	0.993	D	0.725	prob.delet.	None	None	None	None	N
F/S	0.9264	likely_pathogenic	0.8955	pathogenic	-2.565	Highly Destabilizing	0.991	D	0.604	neutral	N	0.490842619	None	None	N
F/T	0.9426	likely_pathogenic	0.9274	pathogenic	-2.221	Highly Destabilizing	0.993	D	0.626	neutral	None	None	None	None	N
F/V	0.5826	likely_pathogenic	0.5407	ambiguous	-0.717	Destabilizing	0.939	D	0.482	neutral	N	0.477610827	None	None	N
F/W	0.7107	likely_pathogenic	0.671	pathogenic	0.395	Stabilizing	0.998	D	0.469	neutral	None	None	None	None	N
F/Y	0.2076	likely_benign	0.1933	benign	0.122	Stabilizing	0.02	N	0.227	neutral	N	0.439612586	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.