TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30596	92011;92012;92013	chr2:178550052;178550051;178550050	chr2:179414779;179414778;179414777
N2AB	28955	87088;87089;87090	chr2:178550052;178550051;178550050	chr2:179414779;179414778;179414777
N2A	28028	84307;84308;84309	chr2:178550052;178550051;178550050	chr2:179414779;179414778;179414777
N2B	21531	64816;64817;64818	chr2:178550052;178550051;178550050	chr2:179414779;179414778;179414777
Novex-1	21656	65191;65192;65193	chr2:178550052;178550051;178550050	chr2:179414779;179414778;179414777
Novex-2	21723	65392;65393;65394	chr2:178550052;178550051;178550050	chr2:179414779;179414778;179414777
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-149
• Domain position: 65
• Structural Position: 153
• Q(SASA): 0.2941
• 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	None	None	0.027	N	0.493	0.173	0.59408574423	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.1157	likely_benign	0.1316	benign	-1.616	Destabilizing	0.027	N	0.493	neutral	N	0.500811053	None	None	N
V/C	0.4182	ambiguous	0.4495	ambiguous	-1.049	Destabilizing	0.935	D	0.509	neutral	None	None	None	None	N
V/D	0.156	likely_benign	0.1872	benign	-1.477	Destabilizing	0.38	N	0.597	neutral	None	None	None	None	N
V/E	0.1664	likely_benign	0.1945	benign	-1.446	Destabilizing	0.317	N	0.565	neutral	N	0.395433027	None	None	N
V/F	0.0961	likely_benign	0.107	benign	-1.182	Destabilizing	0.235	N	0.533	neutral	None	None	None	None	N
V/G	0.1465	likely_benign	0.1633	benign	-1.973	Destabilizing	0.317	N	0.573	neutral	N	0.48703591	None	None	N
V/H	0.2706	likely_benign	0.3105	benign	-1.525	Destabilizing	0.935	D	0.603	neutral	None	None	None	None	N
V/I	0.0562	likely_benign	0.0574	benign	-0.716	Destabilizing	None	N	0.201	neutral	N	0.452134458	None	None	N
V/K	0.1953	likely_benign	0.2206	benign	-1.225	Destabilizing	0.38	N	0.565	neutral	None	None	None	None	N
V/L	0.0883	likely_benign	0.0903	benign	-0.716	Destabilizing	None	N	0.192	neutral	N	0.482014648	None	None	N
V/M	0.0813	likely_benign	0.0828	benign	-0.545	Destabilizing	0.235	N	0.528	neutral	None	None	None	None	N
V/N	0.0911	likely_benign	0.1048	benign	-1.042	Destabilizing	0.38	N	0.599	neutral	None	None	None	None	N
V/P	0.3698	ambiguous	0.4586	ambiguous	-0.982	Destabilizing	0.555	D	0.582	neutral	None	None	None	None	N
V/Q	0.1863	likely_benign	0.2068	benign	-1.185	Destabilizing	0.555	D	0.591	neutral	None	None	None	None	N
V/R	0.1839	likely_benign	0.2077	benign	-0.762	Destabilizing	0.38	N	0.601	neutral	None	None	None	None	N
V/S	0.105	likely_benign	0.1204	benign	-1.615	Destabilizing	0.081	N	0.534	neutral	None	None	None	None	N
V/T	0.0941	likely_benign	0.1013	benign	-1.472	Destabilizing	0.002	N	0.349	neutral	None	None	None	None	N
V/W	0.5246	ambiguous	0.5642	pathogenic	-1.411	Destabilizing	0.935	D	0.631	neutral	None	None	None	None	N
V/Y	0.2784	likely_benign	0.3013	benign	-1.111	Destabilizing	0.555	D	0.537	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.