TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30858	92797;92798;92799	chr2:178549054;178549053;178549052	chr2:179413781;179413780;179413779
N2AB	29217	87874;87875;87876	chr2:178549054;178549053;178549052	chr2:179413781;179413780;179413779
N2A	28290	85093;85094;85095	chr2:178549054;178549053;178549052	chr2:179413781;179413780;179413779
N2B	21793	65602;65603;65604	chr2:178549054;178549053;178549052	chr2:179413781;179413780;179413779
Novex-1	21918	65977;65978;65979	chr2:178549054;178549053;178549052	chr2:179413781;179413780;179413779
Novex-2	21985	66178;66179;66180	chr2:178549054;178549053;178549052	chr2:179413781;179413780;179413779
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: Fn3-113
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0678
• 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	rs1463927651	-3.402	0.822	D	0.719	0.487	0.83593546449	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/T	rs1463927651	-3.402	0.822	D	0.719	0.487	0.83593546449	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs1463927651	-3.402	0.822	D	0.719	0.487	0.83593546449	gnomAD-4.0.0	4.33767E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69515E-06	5.48944E-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
I/A	0.7725	likely_pathogenic	0.7286	pathogenic	-3.045	Highly Destabilizing	0.754	D	0.682	prob.neutral	None	None	None	None	N
I/C	0.9567	likely_pathogenic	0.9525	pathogenic	-2.163	Highly Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
I/D	0.9989	likely_pathogenic	0.998	pathogenic	-3.767	Highly Destabilizing	0.993	D	0.881	deleterious	None	None	None	None	N
I/E	0.9956	likely_pathogenic	0.9929	pathogenic	-3.447	Highly Destabilizing	0.978	D	0.877	deleterious	None	None	None	None	N
I/F	0.7467	likely_pathogenic	0.7385	pathogenic	-1.832	Destabilizing	0.942	D	0.635	neutral	D	0.524277469	None	None	N
I/G	0.9894	likely_pathogenic	0.9846	pathogenic	-3.637	Highly Destabilizing	0.978	D	0.877	deleterious	None	None	None	None	N
I/H	0.9965	likely_pathogenic	0.9947	pathogenic	-3.282	Highly Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
I/K	0.9925	likely_pathogenic	0.9888	pathogenic	-2.411	Highly Destabilizing	0.978	D	0.877	deleterious	None	None	None	None	N
I/L	0.2436	likely_benign	0.218	benign	-1.247	Destabilizing	0.294	N	0.317	neutral	N	0.481486212	None	None	N
I/M	0.3248	likely_benign	0.3078	benign	-1.396	Destabilizing	0.942	D	0.647	neutral	N	0.503450962	None	None	N
I/N	0.9885	likely_pathogenic	0.9811	pathogenic	-3.128	Highly Destabilizing	0.99	D	0.896	deleterious	D	0.535887264	None	None	N
I/P	0.9841	likely_pathogenic	0.9771	pathogenic	-1.84	Destabilizing	0.993	D	0.891	deleterious	None	None	None	None	N
I/Q	0.9937	likely_pathogenic	0.9901	pathogenic	-2.786	Highly Destabilizing	0.993	D	0.895	deleterious	None	None	None	None	N
I/R	0.9876	likely_pathogenic	0.9814	pathogenic	-2.385	Highly Destabilizing	0.978	D	0.897	deleterious	None	None	None	None	N
I/S	0.9519	likely_pathogenic	0.9342	pathogenic	-3.647	Highly Destabilizing	0.942	D	0.839	deleterious	D	0.535887264	None	None	N
I/T	0.6301	likely_pathogenic	0.5623	ambiguous	-3.173	Highly Destabilizing	0.822	D	0.719	prob.delet.	D	0.535633774	None	None	N
I/V	0.0935	likely_benign	0.0944	benign	-1.84	Destabilizing	0.006	N	0.196	neutral	N	0.381062928	None	None	N
I/W	0.994	likely_pathogenic	0.9933	pathogenic	-2.247	Highly Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
I/Y	0.985	likely_pathogenic	0.9827	pathogenic	-2.09	Highly Destabilizing	0.978	D	0.748	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.