TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30736	92431;92432;92433	chr2:178549420;178549419;178549418	chr2:179414147;179414146;179414145
N2AB	29095	87508;87509;87510	chr2:178549420;178549419;178549418	chr2:179414147;179414146;179414145
N2A	28168	84727;84728;84729	chr2:178549420;178549419;178549418	chr2:179414147;179414146;179414145
N2B	21671	65236;65237;65238	chr2:178549420;178549419;178549418	chr2:179414147;179414146;179414145
Novex-1	21796	65611;65612;65613	chr2:178549420;178549419;178549418	chr2:179414147;179414146;179414145
Novex-2	21863	65812;65813;65814	chr2:178549420;178549419;178549418	chr2:179414147;179414146;179414145
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: Fn3-112
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0487
• 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	1.0	N	0.817	0.505	0.701105732878	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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
I/A	0.7361	likely_pathogenic	0.7875	pathogenic	-2.937	Highly Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
I/C	0.8731	likely_pathogenic	0.8999	pathogenic	-2.539	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
I/D	0.9984	likely_pathogenic	0.9987	pathogenic	-3.448	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
I/E	0.9956	likely_pathogenic	0.9962	pathogenic	-3.131	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/F	0.6588	likely_pathogenic	0.7137	pathogenic	-1.769	Destabilizing	1.0	D	0.818	deleterious	N	0.488689799	None	None	N
I/G	0.9778	likely_pathogenic	0.9849	pathogenic	-3.556	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
I/H	0.9943	likely_pathogenic	0.9956	pathogenic	-3.18	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
I/K	0.9932	likely_pathogenic	0.9937	pathogenic	-2.199	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
I/L	0.1878	likely_benign	0.2131	benign	-1.083	Destabilizing	0.993	D	0.344	neutral	N	0.473434372	None	None	N
I/M	0.1756	likely_benign	0.1929	benign	-1.444	Destabilizing	1.0	D	0.799	deleterious	N	0.442946467	None	None	N
I/N	0.9827	likely_pathogenic	0.9834	pathogenic	-2.856	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.525711684	None	None	N
I/P	0.9976	likely_pathogenic	0.9986	pathogenic	-1.691	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/Q	0.9901	likely_pathogenic	0.9911	pathogenic	-2.527	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/R	0.9869	likely_pathogenic	0.9888	pathogenic	-2.196	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/S	0.9427	likely_pathogenic	0.9534	pathogenic	-3.513	Highly Destabilizing	1.0	D	0.844	deleterious	N	0.495744144	None	None	N
I/T	0.9161	likely_pathogenic	0.9278	pathogenic	-3.025	Highly Destabilizing	1.0	D	0.817	deleterious	N	0.498453169	None	None	N
I/V	0.0924	likely_benign	0.1048	benign	-1.691	Destabilizing	0.993	D	0.279	neutral	N	0.420624181	None	None	N
I/W	0.9949	likely_pathogenic	0.9967	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
I/Y	0.9705	likely_pathogenic	0.9759	pathogenic	-1.943	Destabilizing	1.0	D	0.845	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.