TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6474	19645;19646;19647	chr2:178728506;178728505;178728504	chr2:179593233;179593232;179593231
N2AB	6157	18694;18695;18696	chr2:178728506;178728505;178728504	chr2:179593233;179593232;179593231
N2A	5230	15913;15914;15915	chr2:178728506;178728505;178728504	chr2:179593233;179593232;179593231
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-48
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.4804
• 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/M	None	None	0.999	D	0.833	0.73	0.764583988284	gnomAD-4.0.0	1.60553E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88885E-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
V/A	0.9067	likely_pathogenic	0.8778	pathogenic	-1.9	Destabilizing	0.998	D	0.688	prob.neutral	D	0.610392572	None	None	N
V/C	0.9832	likely_pathogenic	0.9801	pathogenic	-1.455	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/D	0.9919	likely_pathogenic	0.9876	pathogenic	-2.173	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/E	0.9785	likely_pathogenic	0.9697	pathogenic	-2.097	Highly Destabilizing	1.0	D	0.818	deleterious	D	0.636303932	None	None	N
V/F	0.8947	likely_pathogenic	0.8684	pathogenic	-1.294	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/G	0.9062	likely_pathogenic	0.8764	pathogenic	-2.298	Highly Destabilizing	1.0	D	0.799	deleterious	D	0.636303932	None	None	N
V/H	0.9954	likely_pathogenic	0.9935	pathogenic	-1.855	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/I	0.14	likely_benign	0.1344	benign	-0.855	Destabilizing	0.813	D	0.567	neutral	None	None	None	None	N
V/K	0.9868	likely_pathogenic	0.9821	pathogenic	-1.533	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/L	0.8444	likely_pathogenic	0.797	pathogenic	-0.855	Destabilizing	0.981	D	0.703	prob.neutral	D	0.55497666	None	None	N
V/M	0.844	likely_pathogenic	0.8221	pathogenic	-0.803	Destabilizing	0.999	D	0.833	deleterious	D	0.635900324	None	None	N
V/N	0.9748	likely_pathogenic	0.9657	pathogenic	-1.496	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/P	0.9752	likely_pathogenic	0.9693	pathogenic	-1.172	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/Q	0.9856	likely_pathogenic	0.9811	pathogenic	-1.588	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/R	0.9803	likely_pathogenic	0.974	pathogenic	-1.112	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/S	0.9495	likely_pathogenic	0.9358	pathogenic	-2.066	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/T	0.9263	likely_pathogenic	0.9044	pathogenic	-1.877	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
V/W	0.9979	likely_pathogenic	0.9968	pathogenic	-1.595	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/Y	0.9864	likely_pathogenic	0.9815	pathogenic	-1.295	Destabilizing	1.0	D	0.819	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.