TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30883	92872;92873;92874	chr2:178548979;178548978;178548977	chr2:179413706;179413705;179413704
N2AB	29242	87949;87950;87951	chr2:178548979;178548978;178548977	chr2:179413706;179413705;179413704
N2A	28315	85168;85169;85170	chr2:178548979;178548978;178548977	chr2:179413706;179413705;179413704
N2B	21818	65677;65678;65679	chr2:178548979;178548978;178548977	chr2:179413706;179413705;179413704
Novex-1	21943	66052;66053;66054	chr2:178548979;178548978;178548977	chr2:179413706;179413705;179413704
Novex-2	22010	66253;66254;66255	chr2:178548979;178548978;178548977	chr2:179413706;179413705;179413704
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-113
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1106
• 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/I	None	None	0.008	N	0.362	0.066	0.37281450598	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	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
V/A	0.4266	ambiguous	0.4387	ambiguous	-1.898	Destabilizing	0.014	N	0.329	neutral	N	0.484747142	None	None	N
V/C	0.9049	likely_pathogenic	0.9111	pathogenic	-1.677	Destabilizing	0.996	D	0.797	deleterious	None	None	None	None	N
V/D	0.9868	likely_pathogenic	0.986	pathogenic	-2.439	Highly Destabilizing	0.901	D	0.851	deleterious	N	0.50499099	None	None	N
V/E	0.9608	likely_pathogenic	0.9577	pathogenic	-2.166	Highly Destabilizing	0.923	D	0.817	deleterious	None	None	None	None	N
V/F	0.6952	likely_pathogenic	0.6485	pathogenic	-1.146	Destabilizing	0.901	D	0.812	deleterious	N	0.504417878	None	None	N
V/G	0.8328	likely_pathogenic	0.8373	pathogenic	-2.493	Highly Destabilizing	0.722	D	0.809	deleterious	D	0.555785036	None	None	N
V/H	0.9854	likely_pathogenic	0.9842	pathogenic	-2.383	Highly Destabilizing	0.996	D	0.855	deleterious	None	None	None	None	N
V/I	0.1005	likely_benign	0.0964	benign	-0.216	Destabilizing	0.008	N	0.362	neutral	N	0.484409087	None	None	N
V/K	0.9653	likely_pathogenic	0.9607	pathogenic	-1.593	Destabilizing	0.923	D	0.818	deleterious	None	None	None	None	N
V/L	0.4669	ambiguous	0.4248	ambiguous	-0.216	Destabilizing	0.156	N	0.679	prob.neutral	N	0.478063828	None	None	N
V/M	0.3841	ambiguous	0.3636	ambiguous	-0.426	Destabilizing	0.923	D	0.707	prob.neutral	None	None	None	None	N
V/N	0.9638	likely_pathogenic	0.9621	pathogenic	-2.053	Highly Destabilizing	0.923	D	0.864	deleterious	None	None	None	None	N
V/P	0.9826	likely_pathogenic	0.9804	pathogenic	-0.75	Destabilizing	0.961	D	0.834	deleterious	None	None	None	None	N
V/Q	0.9519	likely_pathogenic	0.9495	pathogenic	-1.768	Destabilizing	0.961	D	0.838	deleterious	None	None	None	None	N
V/R	0.9531	likely_pathogenic	0.9496	pathogenic	-1.679	Destabilizing	0.961	D	0.865	deleterious	None	None	None	None	N
V/S	0.832	likely_pathogenic	0.8497	pathogenic	-2.71	Highly Destabilizing	0.237	N	0.626	neutral	None	None	None	None	N
V/T	0.7133	likely_pathogenic	0.7207	pathogenic	-2.258	Highly Destabilizing	0.775	D	0.723	prob.delet.	None	None	None	None	N
V/W	0.9936	likely_pathogenic	0.9933	pathogenic	-1.651	Destabilizing	0.996	D	0.836	deleterious	None	None	None	None	N
V/Y	0.9628	likely_pathogenic	0.9592	pathogenic	-1.226	Destabilizing	0.961	D	0.796	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.