TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16050	48373;48374;48375	chr2:178616741;178616740;178616739	chr2:179481468;179481467;179481466
N2AB	14409	43450;43451;43452	chr2:178616741;178616740;178616739	chr2:179481468;179481467;179481466
N2A	13482	40669;40670;40671	chr2:178616741;178616740;178616739	chr2:179481468;179481467;179481466
N2B	6985	21178;21179;21180	chr2:178616741;178616740;178616739	chr2:179481468;179481467;179481466
Novex-1	7110	21553;21554;21555	chr2:178616741;178616740;178616739	chr2:179481468;179481467;179481466
Novex-2	7177	21754;21755;21756	chr2:178616741;178616740;178616739	chr2:179481468;179481467;179481466
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: Ig-109
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.0959
• 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/G	None	None	1.0	D	0.857	0.526	0.715692154805	gnomAD-4.0.0	4.79278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29919E-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	0.9076	likely_pathogenic	0.94	pathogenic	-2.267	Highly Destabilizing	0.999	D	0.657	neutral	D	0.619147926	None	None	N
V/C	0.9605	likely_pathogenic	0.9675	pathogenic	-1.825	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/D	0.9974	likely_pathogenic	0.9986	pathogenic	-3.198	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.620341081	None	None	N
V/E	0.9944	likely_pathogenic	0.9963	pathogenic	-2.939	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/F	0.8995	likely_pathogenic	0.906	pathogenic	-1.365	Destabilizing	1.0	D	0.834	deleterious	D	0.617299527	None	None	N
V/G	0.9443	likely_pathogenic	0.9632	pathogenic	-2.839	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.620341081	None	None	N
V/H	0.9988	likely_pathogenic	0.9991	pathogenic	-2.686	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/I	0.1458	likely_benign	0.1456	benign	-0.64	Destabilizing	0.997	D	0.561	neutral	N	0.450998326	None	None	N
V/K	0.9951	likely_pathogenic	0.9962	pathogenic	-2.015	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/L	0.8275	likely_pathogenic	0.8318	pathogenic	-0.64	Destabilizing	0.997	D	0.673	neutral	N	0.428247074	None	None	N
V/M	0.8318	likely_pathogenic	0.8522	pathogenic	-0.728	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
V/N	0.9932	likely_pathogenic	0.9958	pathogenic	-2.486	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/P	0.9961	likely_pathogenic	0.9969	pathogenic	-1.158	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/Q	0.9942	likely_pathogenic	0.996	pathogenic	-2.262	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/R	0.9886	likely_pathogenic	0.9918	pathogenic	-1.873	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/S	0.9807	likely_pathogenic	0.9879	pathogenic	-3.059	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/T	0.9283	likely_pathogenic	0.9442	pathogenic	-2.653	Highly Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
V/W	0.9986	likely_pathogenic	0.9989	pathogenic	-1.987	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/Y	0.9938	likely_pathogenic	0.9944	pathogenic	-1.592	Destabilizing	1.0	D	0.829	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.