TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15728	47407;47408;47409	chr2:178618276;178618275;178618274	chr2:179483003;179483002;179483001
N2AB	14087	42484;42485;42486	chr2:178618276;178618275;178618274	chr2:179483003;179483002;179483001
N2A	13160	39703;39704;39705	chr2:178618276;178618275;178618274	chr2:179483003;179483002;179483001
N2B	6663	20212;20213;20214	chr2:178618276;178618275;178618274	chr2:179483003;179483002;179483001
Novex-1	6788	20587;20588;20589	chr2:178618276;178618275;178618274	chr2:179483003;179483002;179483001
Novex-2	6855	20788;20789;20790	chr2:178618276;178618275;178618274	chr2:179483003;179483002;179483001
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-1
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1048
• 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/S	rs1559849572	None	1.0	D	0.894	0.911	0.922020344611	gnomAD-4.0.0	1.59324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86221E-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	0.9941	likely_pathogenic	0.9962	pathogenic	-3.037	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/C	0.9689	likely_pathogenic	0.9792	pathogenic	-1.647	Destabilizing	1.0	D	0.874	deleterious	D	0.798424547	None	None	N
Y/D	0.9923	likely_pathogenic	0.9951	pathogenic	-3.665	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.798424547	None	None	N
Y/E	0.9977	likely_pathogenic	0.9983	pathogenic	-3.451	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/F	0.4646	ambiguous	0.4939	ambiguous	-1.138	Destabilizing	0.999	D	0.745	deleterious	D	0.686124502	None	None	N
Y/G	0.9817	likely_pathogenic	0.9887	pathogenic	-3.446	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/H	0.9784	likely_pathogenic	0.9877	pathogenic	-2.171	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.748200625	None	None	N
Y/I	0.971	likely_pathogenic	0.9716	pathogenic	-1.667	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/K	0.9977	likely_pathogenic	0.9982	pathogenic	-2.352	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/L	0.9532	likely_pathogenic	0.9577	pathogenic	-1.667	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
Y/M	0.9812	likely_pathogenic	0.9861	pathogenic	-1.332	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/N	0.9344	likely_pathogenic	0.9654	pathogenic	-3.221	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.798732498	None	None	N
Y/P	0.999	likely_pathogenic	0.9992	pathogenic	-2.141	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9983	pathogenic	-2.939	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/R	0.9957	likely_pathogenic	0.9965	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/S	0.9807	likely_pathogenic	0.989	pathogenic	-3.481	Highly Destabilizing	1.0	D	0.894	deleterious	D	0.798424547	None	None	N
Y/T	0.9896	likely_pathogenic	0.9931	pathogenic	-3.148	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/V	0.9466	likely_pathogenic	0.9502	pathogenic	-2.141	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/W	0.9381	likely_pathogenic	0.9472	pathogenic	-0.475	Destabilizing	1.0	D	0.819	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.