TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32534	97825;97826;97827	chr2:178541477;178541476;178541475	chr2:179406204;179406203;179406202
N2AB	30893	92902;92903;92904	chr2:178541477;178541476;178541475	chr2:179406204;179406203;179406202
N2A	29966	90121;90122;90123	chr2:178541477;178541476;178541475	chr2:179406204;179406203;179406202
N2B	23469	70630;70631;70632	chr2:178541477;178541476;178541475	chr2:179406204;179406203;179406202
Novex-1	23594	71005;71006;71007	chr2:178541477;178541476;178541475	chr2:179406204;179406203;179406202
Novex-2	23661	71206;71207;71208	chr2:178541477;178541476;178541475	chr2:179406204;179406203;179406202
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-125
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1223
• 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
Y/H	None	None	1.0	D	0.795	0.857	0.756779391194	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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
Y/A	0.9962	likely_pathogenic	0.9962	pathogenic	-3.789	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/C	0.8766	likely_pathogenic	0.8779	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.864	deleterious	D	0.650941024	None	None	N
Y/D	0.9945	likely_pathogenic	0.9949	pathogenic	-4.013	Highly Destabilizing	1.0	D	0.904	deleterious	D	0.651344632	None	None	N
Y/E	0.9987	likely_pathogenic	0.9987	pathogenic	-3.802	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/F	0.1422	likely_benign	0.1479	benign	-1.575	Destabilizing	0.999	D	0.645	neutral	D	0.56268989	None	None	N
Y/G	0.9888	likely_pathogenic	0.9882	pathogenic	-4.181	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
Y/H	0.9565	likely_pathogenic	0.9635	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.650941024	None	None	N
Y/I	0.972	likely_pathogenic	0.9701	pathogenic	-2.446	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/K	0.998	likely_pathogenic	0.9983	pathogenic	-2.742	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/L	0.9556	likely_pathogenic	0.9525	pathogenic	-2.446	Highly Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
Y/M	0.9783	likely_pathogenic	0.9766	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/N	0.96	likely_pathogenic	0.9644	pathogenic	-3.506	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.651344632	None	None	N
Y/P	0.9994	likely_pathogenic	0.9995	pathogenic	-2.915	Highly Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9974	pathogenic	-3.257	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/R	0.9936	likely_pathogenic	0.9938	pathogenic	-2.43	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/S	0.9845	likely_pathogenic	0.985	pathogenic	-3.814	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.635093107	None	None	N
Y/T	0.9958	likely_pathogenic	0.9956	pathogenic	-3.493	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/V	0.9613	likely_pathogenic	0.9585	pathogenic	-2.915	Highly Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
Y/W	0.7885	likely_pathogenic	0.7863	pathogenic	-0.778	Destabilizing	1.0	D	0.785	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.