TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35182	105769;105770;105771	chr2:178531071;178531070;178531069	chr2:179395798;179395797;179395796
N2AB	33541	100846;100847;100848	chr2:178531071;178531070;178531069	chr2:179395798;179395797;179395796
N2A	32614	98065;98066;98067	chr2:178531071;178531070;178531069	chr2:179395798;179395797;179395796
N2B	26117	78574;78575;78576	chr2:178531071;178531070;178531069	chr2:179395798;179395797;179395796
Novex-1	26242	78949;78950;78951	chr2:178531071;178531070;178531069	chr2:179395798;179395797;179395796
Novex-2	26309	79150;79151;79152	chr2:178531071;178531070;178531069	chr2:179395798;179395797;179395796
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: Ig-164
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.2828
• 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/C	rs878913505	None	1.0	N	0.694	0.582	None	gnomAD-4.0.0	2.73654E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59756E-06	0	0
Y/H	rs886042549	None	0.999	D	0.643	0.562	0.481988042695	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
Y/A	0.9637	likely_pathogenic	0.9529	pathogenic	-1.393	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
Y/C	0.8195	likely_pathogenic	0.7668	pathogenic	-0.218	Destabilizing	1.0	D	0.694	prob.neutral	N	0.483895584	None	None	N
Y/D	0.8813	likely_pathogenic	0.8248	pathogenic	0.412	Stabilizing	0.999	D	0.733	prob.delet.	N	0.411074483	None	None	N
Y/E	0.9752	likely_pathogenic	0.9626	pathogenic	0.436	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
Y/F	0.3048	likely_benign	0.2628	benign	-0.663	Destabilizing	0.997	D	0.587	neutral	D	0.530864601	None	None	N
Y/G	0.8812	likely_pathogenic	0.8355	pathogenic	-1.648	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
Y/H	0.8209	likely_pathogenic	0.7476	pathogenic	-0.351	Destabilizing	0.999	D	0.643	neutral	D	0.524765348	None	None	N
Y/I	0.9564	likely_pathogenic	0.9473	pathogenic	-0.685	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
Y/K	0.9758	likely_pathogenic	0.9628	pathogenic	-0.311	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
Y/L	0.8866	likely_pathogenic	0.8648	pathogenic	-0.685	Destabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	N
Y/M	0.9554	likely_pathogenic	0.9411	pathogenic	-0.414	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
Y/N	0.7044	likely_pathogenic	0.5993	pathogenic	-0.488	Destabilizing	0.999	D	0.728	prob.delet.	N	0.465658329	None	None	N
Y/P	0.9909	likely_pathogenic	0.9907	pathogenic	-0.907	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
Y/Q	0.9662	likely_pathogenic	0.9501	pathogenic	-0.437	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
Y/R	0.9443	likely_pathogenic	0.9206	pathogenic	0.023	Stabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
Y/S	0.8737	likely_pathogenic	0.8205	pathogenic	-0.998	Destabilizing	0.999	D	0.749	deleterious	N	0.485764243	None	None	N
Y/T	0.9595	likely_pathogenic	0.9391	pathogenic	-0.88	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
Y/V	0.9156	likely_pathogenic	0.8987	pathogenic	-0.907	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
Y/W	0.7684	likely_pathogenic	0.7523	pathogenic	-0.558	Destabilizing	1.0	D	0.602	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.