TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34289	103090;103091;103092	chr2:178533750;178533749;178533748	chr2:179398477;179398476;179398475
N2AB	32648	98167;98168;98169	chr2:178533750;178533749;178533748	chr2:179398477;179398476;179398475
N2A	31721	95386;95387;95388	chr2:178533750;178533749;178533748	chr2:179398477;179398476;179398475
N2B	25224	75895;75896;75897	chr2:178533750;178533749;178533748	chr2:179398477;179398476;179398475
Novex-1	25349	76270;76271;76272	chr2:178533750;178533749;178533748	chr2:179398477;179398476;179398475
Novex-2	25416	76471;76472;76473	chr2:178533750;178533749;178533748	chr2:179398477;179398476;179398475
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-161
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2118
• 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
V/A	rs1370660271	-1.753	0.939	D	0.655	0.752	0.792328519658	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
V/A	rs1370660271	-1.753	0.939	D	0.655	0.752	0.792328519658	gnomAD-4.0.0	3.18196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85768E-06	0	3.02389E-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
V/A	0.815	likely_pathogenic	0.8443	pathogenic	-1.744	Destabilizing	0.939	D	0.655	neutral	D	0.588247644	None	None	N
V/C	0.934	likely_pathogenic	0.9548	pathogenic	-1.126	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
V/D	0.9918	likely_pathogenic	0.993	pathogenic	-1.901	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
V/E	0.9765	likely_pathogenic	0.9793	pathogenic	-1.745	Destabilizing	0.997	D	0.831	deleterious	D	0.626635174	None	None	N
V/F	0.6756	likely_pathogenic	0.736	pathogenic	-1.113	Destabilizing	0.986	D	0.729	prob.delet.	None	None	None	None	N
V/G	0.9205	likely_pathogenic	0.9319	pathogenic	-2.198	Highly Destabilizing	0.997	D	0.839	deleterious	D	0.626635174	None	None	N
V/H	0.9904	likely_pathogenic	0.9932	pathogenic	-1.737	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
V/I	0.0878	likely_benign	0.092	benign	-0.519	Destabilizing	0.17	N	0.265	neutral	N	0.463186532	None	None	N
V/K	0.9676	likely_pathogenic	0.9745	pathogenic	-1.381	Destabilizing	0.993	D	0.831	deleterious	None	None	None	None	N
V/L	0.4527	ambiguous	0.4932	ambiguous	-0.519	Destabilizing	0.046	N	0.303	neutral	D	0.537878633	None	None	N
V/M	0.487	ambiguous	0.5595	ambiguous	-0.471	Destabilizing	0.986	D	0.662	neutral	None	None	None	None	N
V/N	0.9778	likely_pathogenic	0.983	pathogenic	-1.49	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
V/P	0.9645	likely_pathogenic	0.9724	pathogenic	-0.898	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
V/Q	0.9708	likely_pathogenic	0.9758	pathogenic	-1.437	Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	N
V/R	0.9561	likely_pathogenic	0.9639	pathogenic	-1.136	Destabilizing	0.993	D	0.84	deleterious	None	None	None	None	N
V/S	0.9489	likely_pathogenic	0.9615	pathogenic	-2.076	Highly Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
V/T	0.8168	likely_pathogenic	0.8497	pathogenic	-1.777	Destabilizing	0.976	D	0.701	prob.neutral	None	None	None	None	N
V/W	0.9904	likely_pathogenic	0.9942	pathogenic	-1.461	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
V/Y	0.9689	likely_pathogenic	0.9773	pathogenic	-1.086	Destabilizing	0.993	D	0.712	prob.delet.	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.