TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30329	91210;91211;91212	chr2:178551915;178551914;178551913	chr2:179416642;179416641;179416640
N2AB	28688	86287;86288;86289	chr2:178551915;178551914;178551913	chr2:179416642;179416641;179416640
N2A	27761	83506;83507;83508	chr2:178551915;178551914;178551913	chr2:179416642;179416641;179416640
N2B	21264	64015;64016;64017	chr2:178551915;178551914;178551913	chr2:179416642;179416641;179416640
Novex-1	21389	64390;64391;64392	chr2:178551915;178551914;178551913	chr2:179416642;179416641;179416640
Novex-2	21456	64591;64592;64593	chr2:178551915;178551914;178551913	chr2:179416642;179416641;179416640
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-109
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.1663
• 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
G/R	rs1178018014	-1.042	1.0	N	0.907	0.441	0.60359086051	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
G/R	rs1178018014	-1.042	1.0	N	0.907	0.441	0.60359086051	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	7.32654E-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
G/A	0.221	likely_benign	0.2627	benign	-0.848	Destabilizing	0.974	D	0.509	neutral	N	0.508629954	None	None	N
G/C	0.3981	ambiguous	0.4608	ambiguous	-1.185	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
G/D	0.7426	likely_pathogenic	0.7688	pathogenic	-2.198	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
G/E	0.635	likely_pathogenic	0.6761	pathogenic	-2.158	Highly Destabilizing	1.0	D	0.882	deleterious	N	0.492350993	None	None	N
G/F	0.8915	likely_pathogenic	0.9195	pathogenic	-0.993	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
G/H	0.7932	likely_pathogenic	0.8312	pathogenic	-1.821	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
G/I	0.7218	likely_pathogenic	0.8029	pathogenic	-0.149	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
G/K	0.7705	likely_pathogenic	0.819	pathogenic	-1.473	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
G/L	0.7099	likely_pathogenic	0.7608	pathogenic	-0.149	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
G/M	0.7717	likely_pathogenic	0.8138	pathogenic	-0.219	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
G/N	0.6459	likely_pathogenic	0.6772	pathogenic	-1.389	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/P	0.9314	likely_pathogenic	0.9487	pathogenic	-0.34	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
G/Q	0.599	likely_pathogenic	0.6445	pathogenic	-1.442	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
G/R	0.6095	likely_pathogenic	0.687	pathogenic	-1.325	Destabilizing	1.0	D	0.907	deleterious	N	0.466707522	None	None	N
G/S	0.1573	likely_benign	0.1783	benign	-1.608	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
G/T	0.3546	ambiguous	0.4062	ambiguous	-1.487	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/V	0.5346	ambiguous	0.6251	pathogenic	-0.34	Destabilizing	1.0	D	0.883	deleterious	N	0.471977896	None	None	N
G/W	0.836	likely_pathogenic	0.8865	pathogenic	-1.608	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/Y	0.8295	likely_pathogenic	0.8782	pathogenic	-1.113	Destabilizing	1.0	D	0.898	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.