TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5575	16948;16949;16950	chr2:178732246;178732245;178732244	chr2:179596973;179596972;179596971
N2AB	5258	15997;15998;15999	chr2:178732246;178732245;178732244	chr2:179596973;179596972;179596971
N2A	4331	13216;13217;13218	chr2:178732246;178732245;178732244	chr2:179596973;179596972;179596971
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-39
• Domain position: 33
• Structural Position: 46
• Q(SASA): 0.1849
• 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/L	rs1253223397	-0.591	0.099	D	0.459	0.272	0.478980160563	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
I/L	rs1253223397	-0.591	0.099	D	0.459	0.272	0.478980160563	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/L	rs1253223397	-0.591	0.099	D	0.459	0.272	0.478980160563	gnomAD-4.0.0	1.36841E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79894E-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	0.6847	likely_pathogenic	0.7125	pathogenic	-2.197	Highly Destabilizing	0.25	N	0.644	neutral	None	None	None	None	N
I/C	0.8109	likely_pathogenic	0.8384	pathogenic	-1.303	Destabilizing	0.977	D	0.691	prob.neutral	None	None	None	None	N
I/D	0.9636	likely_pathogenic	0.9695	pathogenic	-2.124	Highly Destabilizing	0.972	D	0.806	deleterious	None	None	None	None	N
I/E	0.9241	likely_pathogenic	0.929	pathogenic	-1.956	Destabilizing	0.92	D	0.775	deleterious	None	None	None	None	N
I/F	0.2843	likely_benign	0.3055	benign	-1.306	Destabilizing	0.002	N	0.331	neutral	None	None	None	None	N
I/G	0.8987	likely_pathogenic	0.9144	pathogenic	-2.681	Highly Destabilizing	0.92	D	0.768	deleterious	None	None	None	None	N
I/H	0.902	likely_pathogenic	0.9137	pathogenic	-1.935	Destabilizing	0.992	D	0.804	deleterious	None	None	None	None	N
I/K	0.8355	likely_pathogenic	0.8404	pathogenic	-1.617	Destabilizing	0.896	D	0.777	deleterious	D	0.542676391	None	None	N
I/L	0.1712	likely_benign	0.1937	benign	-0.837	Destabilizing	0.099	N	0.459	neutral	D	0.540375092	None	None	N
I/M	0.1231	likely_benign	0.1272	benign	-0.652	Destabilizing	0.81	D	0.603	neutral	N	0.521596395	None	None	N
I/N	0.6821	likely_pathogenic	0.7044	pathogenic	-1.767	Destabilizing	0.972	D	0.814	deleterious	None	None	None	None	N
I/P	0.879	likely_pathogenic	0.8948	pathogenic	-1.268	Destabilizing	0.972	D	0.817	deleterious	None	None	None	None	N
I/Q	0.8741	likely_pathogenic	0.882	pathogenic	-1.728	Destabilizing	0.972	D	0.81	deleterious	None	None	None	None	N
I/R	0.8158	likely_pathogenic	0.8276	pathogenic	-1.233	Destabilizing	0.896	D	0.813	deleterious	D	0.531320085	None	None	N
I/S	0.7392	likely_pathogenic	0.7604	pathogenic	-2.45	Highly Destabilizing	0.617	D	0.763	deleterious	None	None	None	None	N
I/T	0.5778	likely_pathogenic	0.5743	pathogenic	-2.14	Highly Destabilizing	0.549	D	0.665	neutral	D	0.524065157	None	None	N
I/V	0.0876	likely_benign	0.0896	benign	-1.268	Destabilizing	0.002	N	0.201	neutral	N	0.421592547	None	None	N
I/W	0.9135	likely_pathogenic	0.9283	pathogenic	-1.585	Destabilizing	0.992	D	0.798	deleterious	None	None	None	None	N
I/Y	0.7215	likely_pathogenic	0.7497	pathogenic	-1.293	Destabilizing	0.447	N	0.685	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.