TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21343	64252;64253;64254	chr2:178587184;178587183;178587182	chr2:179451911;179451910;179451909
N2AB	19702	59329;59330;59331	chr2:178587184;178587183;178587182	chr2:179451911;179451910;179451909
N2A	18775	56548;56549;56550	chr2:178587184;178587183;178587182	chr2:179451911;179451910;179451909
N2B	12278	37057;37058;37059	chr2:178587184;178587183;178587182	chr2:179451911;179451910;179451909
Novex-1	12403	37432;37433;37434	chr2:178587184;178587183;178587182	chr2:179451911;179451910;179451909
Novex-2	12470	37633;37634;37635	chr2:178587184;178587183;178587182	chr2:179451911;179451910;179451909
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: Fn3-42
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.1601
• 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	0.987	D	0.495	0.284	0.649263682055	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
V/L	None	None	0.973	N	0.458	0.315	0.599559242703	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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	0.3787	ambiguous	0.3704	ambiguous	-2.015	Highly Destabilizing	0.973	D	0.455	neutral	N	0.487140225	None	None	N
V/C	0.731	likely_pathogenic	0.7247	pathogenic	-2.0	Highly Destabilizing	0.269	N	0.344	neutral	None	None	None	None	N
V/D	0.9162	likely_pathogenic	0.8791	pathogenic	-3.273	Highly Destabilizing	0.999	D	0.819	deleterious	D	0.527022492	None	None	N
V/E	0.5504	ambiguous	0.516	ambiguous	-3.124	Highly Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/F	0.4154	ambiguous	0.3804	ambiguous	-1.215	Destabilizing	0.999	D	0.763	deleterious	N	0.497775742	None	None	N
V/G	0.6399	likely_pathogenic	0.5902	pathogenic	-2.43	Highly Destabilizing	0.998	D	0.744	deleterious	N	0.508829332	None	None	N
V/H	0.862	likely_pathogenic	0.8396	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/I	0.0966	likely_benign	0.1021	benign	-0.879	Destabilizing	0.987	D	0.495	neutral	D	0.525413135	None	None	N
V/K	0.7353	likely_pathogenic	0.7057	pathogenic	-1.709	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/L	0.4957	ambiguous	0.4526	ambiguous	-0.879	Destabilizing	0.973	D	0.458	neutral	N	0.4935061	None	None	N
V/M	0.2427	likely_benign	0.2459	benign	-1.167	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
V/N	0.7492	likely_pathogenic	0.7039	pathogenic	-2.043	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/P	0.9942	likely_pathogenic	0.992	pathogenic	-1.233	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/Q	0.5368	ambiguous	0.5247	ambiguous	-2.005	Highly Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
V/R	0.6682	likely_pathogenic	0.6265	pathogenic	-1.417	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/S	0.4954	ambiguous	0.4716	ambiguous	-2.474	Highly Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
V/T	0.3713	ambiguous	0.3712	ambiguous	-2.214	Highly Destabilizing	0.996	D	0.527	neutral	None	None	None	None	N
V/W	0.9589	likely_pathogenic	0.9522	pathogenic	-1.707	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
V/Y	0.8296	likely_pathogenic	0.794	pathogenic	-1.394	Destabilizing	1.0	D	0.767	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.