TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23505	70738;70739;70740	chr2:178575619;178575618;178575617	chr2:179440346;179440345;179440344
N2AB	21864	65815;65816;65817	chr2:178575619;178575618;178575617	chr2:179440346;179440345;179440344
N2A	20937	63034;63035;63036	chr2:178575619;178575618;178575617	chr2:179440346;179440345;179440344
N2B	14440	43543;43544;43545	chr2:178575619;178575618;178575617	chr2:179440346;179440345;179440344
Novex-1	14565	43918;43919;43920	chr2:178575619;178575618;178575617	chr2:179440346;179440345;179440344
Novex-2	14632	44119;44120;44121	chr2:178575619;178575618;178575617	chr2:179440346;179440345;179440344
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: Fn3-58
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.123
• 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/D	None	None	1.0	D	0.86	0.887	0.895123102283	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9926	likely_pathogenic	0.9936	pathogenic	-3.337	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/C	0.9349	likely_pathogenic	0.9352	pathogenic	-1.971	Destabilizing	1.0	D	0.851	deleterious	D	0.662256321	None	None	N
Y/D	0.9935	likely_pathogenic	0.9941	pathogenic	-3.582	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.694295043	None	None	N
Y/E	0.9984	likely_pathogenic	0.9987	pathogenic	-3.385	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/F	0.2272	likely_benign	0.2253	benign	-1.239	Destabilizing	0.999	D	0.771	deleterious	D	0.641634745	None	None	N
Y/G	0.9833	likely_pathogenic	0.9861	pathogenic	-3.75	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/H	0.9628	likely_pathogenic	0.9558	pathogenic	-2.228	Highly Destabilizing	1.0	D	0.826	deleterious	D	0.694295043	None	None	N
Y/I	0.9647	likely_pathogenic	0.9688	pathogenic	-1.958	Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
Y/K	0.9984	likely_pathogenic	0.9987	pathogenic	-2.382	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/L	0.9604	likely_pathogenic	0.9663	pathogenic	-1.958	Destabilizing	0.997	D	0.811	deleterious	None	None	None	None	N
Y/M	0.9797	likely_pathogenic	0.9813	pathogenic	-1.647	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/N	0.9413	likely_pathogenic	0.9447	pathogenic	-3.138	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.694093238	None	None	N
Y/P	0.9992	likely_pathogenic	0.9994	pathogenic	-2.434	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/Q	0.9971	likely_pathogenic	0.9975	pathogenic	-2.917	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/R	0.9961	likely_pathogenic	0.9965	pathogenic	-2.044	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/S	0.9779	likely_pathogenic	0.9814	pathogenic	-3.508	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.694295043	None	None	N
Y/T	0.9899	likely_pathogenic	0.9919	pathogenic	-3.195	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/V	0.9376	likely_pathogenic	0.9451	pathogenic	-2.434	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/W	0.8732	likely_pathogenic	0.8637	pathogenic	-0.543	Destabilizing	1.0	D	0.799	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.