TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2738	8437;8438;8439	chr2:178770580;178770579;178770578	chr2:179635307;179635306;179635305
N2AB	2738	8437;8438;8439	chr2:178770580;178770579;178770578	chr2:179635307;179635306;179635305
N2A	2738	8437;8438;8439	chr2:178770580;178770579;178770578	chr2:179635307;179635306;179635305
N2B	2692	8299;8300;8301	chr2:178770580;178770579;178770578	chr2:179635307;179635306;179635305
Novex-1	2692	8299;8300;8301	chr2:178770580;178770579;178770578	chr2:179635307;179635306;179635305
Novex-2	2692	8299;8300;8301	chr2:178770580;178770579;178770578	chr2:179635307;179635306;179635305
Novex-3	2738	8437;8438;8439	chr2:178770580;178770579;178770578	chr2:179635307;179635306;179635305

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-17
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.04
• 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	rs1340253990	None	0.27	D	0.5	0.18	0.58895048698	gnomAD-4.0.0	1.59052E-06	None	None	None	None	N	None	0	0	None	4.76554E-05	0	None	0	0	0	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	0.1342	likely_benign	0.2162	benign	-1.745	Destabilizing	0.001	N	0.285	neutral	D	0.525499965	None	None	N
V/C	0.7017	likely_pathogenic	0.794	pathogenic	-1.279	Destabilizing	0.944	D	0.738	prob.delet.	None	None	None	None	N
V/D	0.5576	ambiguous	0.7832	pathogenic	-1.82	Destabilizing	0.642	D	0.739	prob.delet.	D	0.655337747	None	None	N
V/E	0.4675	ambiguous	0.6761	pathogenic	-1.637	Destabilizing	0.704	D	0.693	prob.neutral	None	None	None	None	N
V/F	0.2263	likely_benign	0.3342	benign	-1.09	Destabilizing	0.863	D	0.728	prob.delet.	D	0.616840266	None	None	N
V/G	0.2219	likely_benign	0.3705	ambiguous	-2.186	Highly Destabilizing	0.002	N	0.526	neutral	D	0.615371689	None	None	N
V/H	0.7235	likely_pathogenic	0.8598	pathogenic	-1.544	Destabilizing	0.981	D	0.803	deleterious	None	None	None	None	N
V/I	0.0843	likely_benign	0.0892	benign	-0.536	Destabilizing	0.27	N	0.5	neutral	D	0.527957686	None	None	N
V/K	0.5395	ambiguous	0.7386	pathogenic	-1.328	Destabilizing	0.704	D	0.695	prob.neutral	None	None	None	None	N
V/L	0.2484	likely_benign	0.3616	ambiguous	-0.536	Destabilizing	0.002	N	0.278	neutral	D	0.593517029	None	None	N
V/M	0.1667	likely_benign	0.2235	benign	-0.666	Destabilizing	0.893	D	0.629	neutral	None	None	None	None	N
V/N	0.4042	ambiguous	0.6047	pathogenic	-1.58	Destabilizing	0.704	D	0.735	prob.delet.	None	None	None	None	N
V/P	0.571	likely_pathogenic	0.7437	pathogenic	-0.913	Destabilizing	0.828	D	0.741	deleterious	None	None	None	None	N
V/Q	0.4818	ambiguous	0.6635	pathogenic	-1.469	Destabilizing	0.944	D	0.769	deleterious	None	None	None	None	N
V/R	0.5117	ambiguous	0.7061	pathogenic	-1.163	Destabilizing	0.828	D	0.769	deleterious	None	None	None	None	N
V/S	0.2048	likely_benign	0.3357	benign	-2.18	Highly Destabilizing	0.037	N	0.491	neutral	None	None	None	None	N
V/T	0.199	likely_benign	0.289	benign	-1.847	Destabilizing	0.329	N	0.493	neutral	None	None	None	None	N
V/W	0.8608	likely_pathogenic	0.9325	pathogenic	-1.345	Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	N
V/Y	0.6333	likely_pathogenic	0.792	pathogenic	-0.998	Destabilizing	0.944	D	0.733	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.