TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22851	68776;68777;68778	chr2:178577875;178577874;178577873	chr2:179442602;179442601;179442600
N2AB	21210	63853;63854;63855	chr2:178577875;178577874;178577873	chr2:179442602;179442601;179442600
N2A	20283	61072;61073;61074	chr2:178577875;178577874;178577873	chr2:179442602;179442601;179442600
N2B	13786	41581;41582;41583	chr2:178577875;178577874;178577873	chr2:179442602;179442601;179442600
Novex-1	13911	41956;41957;41958	chr2:178577875;178577874;178577873	chr2:179442602;179442601;179442600
Novex-2	13978	42157;42158;42159	chr2:178577875;178577874;178577873	chr2:179442602;179442601;179442600
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-54
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.6247
• 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
I/T	None	None	0.892	N	0.625	0.34	0.6596391	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
I/V	None	None	0.011	N	0.184	0.083	0.40694574	gnomAD-4.0.0	1.66115E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.13952E-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
I/A	0.4728	ambiguous	0.5512	ambiguous	-0.849	Destabilizing	0.845	D	0.542	neutral	None	None	None	None	N
I/C	0.6968	likely_pathogenic	0.7589	pathogenic	-0.77	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
I/D	0.8462	likely_pathogenic	0.8809	pathogenic	-0.316	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	N
I/E	0.6686	likely_pathogenic	0.7381	pathogenic	-0.381	Destabilizing	0.987	D	0.733	prob.delet.	None	None	None	None	N
I/F	0.2221	likely_benign	0.258	benign	-0.674	Destabilizing	0.967	D	0.581	neutral	N	0.47106606	None	None	N
I/G	0.7504	likely_pathogenic	0.8075	pathogenic	-1.05	Destabilizing	0.987	D	0.728	prob.delet.	None	None	None	None	N
I/H	0.635	likely_pathogenic	0.7022	pathogenic	-0.2	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
I/K	0.4637	ambiguous	0.5273	ambiguous	-0.549	Destabilizing	0.987	D	0.731	prob.delet.	None	None	None	None	N
I/L	0.1188	likely_benign	0.1308	benign	-0.424	Destabilizing	0.426	N	0.255	neutral	N	0.4117754	None	None	N
I/M	0.1014	likely_benign	0.1122	benign	-0.491	Destabilizing	0.983	D	0.557	neutral	N	0.5028774	None	None	N
I/N	0.436	ambiguous	0.507	ambiguous	-0.432	Destabilizing	0.994	D	0.735	prob.delet.	N	0.47482505	None	None	N
I/P	0.9273	likely_pathogenic	0.9427	pathogenic	-0.532	Destabilizing	0.996	D	0.74	deleterious	None	None	None	None	N
I/Q	0.5046	ambiguous	0.5793	pathogenic	-0.633	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	N
I/R	0.3979	ambiguous	0.4618	ambiguous	0.047	Stabilizing	0.987	D	0.735	prob.delet.	None	None	None	None	N
I/S	0.4123	ambiguous	0.4893	ambiguous	-0.922	Destabilizing	0.983	D	0.675	neutral	N	0.4660284	None	None	N
I/T	0.2323	likely_benign	0.2906	benign	-0.874	Destabilizing	0.892	D	0.625	neutral	N	0.41167662	None	None	N
I/V	0.0956	likely_benign	0.1127	benign	-0.532	Destabilizing	0.011	N	0.184	neutral	N	0.42264578	None	None	N
I/W	0.7839	likely_pathogenic	0.8033	pathogenic	-0.687	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
I/Y	0.5945	likely_pathogenic	0.6412	pathogenic	-0.457	Destabilizing	0.987	D	0.689	prob.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.