TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32029	96310;96311;96312	chr2:178544059;178544058;178544057	chr2:179408786;179408785;179408784
N2AB	30388	91387;91388;91389	chr2:178544059;178544058;178544057	chr2:179408786;179408785;179408784
N2A	29461	88606;88607;88608	chr2:178544059;178544058;178544057	chr2:179408786;179408785;179408784
N2B	22964	69115;69116;69117	chr2:178544059;178544058;178544057	chr2:179408786;179408785;179408784
Novex-1	23089	69490;69491;69492	chr2:178544059;178544058;178544057	chr2:179408786;179408785;179408784
Novex-2	23156	69691;69692;69693	chr2:178544059;178544058;178544057	chr2:179408786;179408785;179408784
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-153
• Domain position: 13
• Structural Position: 24
• Q(SASA): 0.312
• Predicted PPI site: I

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	rs897097275	None	1.0	D	0.891	0.731	0.843450473141	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
G/R	rs897097275	None	1.0	D	0.891	0.731	0.843450473141	gnomAD-4.0.0	1.59182E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85941E-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
G/A	0.4823	ambiguous	0.4488	ambiguous	-0.272	Destabilizing	1.0	D	0.785	deleterious	D	0.630094413	None	None	I
G/C	0.6099	likely_pathogenic	0.5749	pathogenic	-0.874	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
G/D	0.7736	likely_pathogenic	0.7507	pathogenic	-0.49	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
G/E	0.8417	likely_pathogenic	0.8173	pathogenic	-0.648	Destabilizing	1.0	D	0.867	deleterious	D	0.61057294	None	None	I
G/F	0.9514	likely_pathogenic	0.9386	pathogenic	-0.967	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
G/H	0.8768	likely_pathogenic	0.8585	pathogenic	-0.509	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
G/I	0.9546	likely_pathogenic	0.9422	pathogenic	-0.383	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	I
G/K	0.916	likely_pathogenic	0.8997	pathogenic	-0.797	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/L	0.9049	likely_pathogenic	0.8843	pathogenic	-0.383	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
G/M	0.9106	likely_pathogenic	0.8905	pathogenic	-0.431	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/N	0.6487	likely_pathogenic	0.6249	pathogenic	-0.459	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
G/P	0.9938	likely_pathogenic	0.9919	pathogenic	-0.312	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/Q	0.8177	likely_pathogenic	0.788	pathogenic	-0.733	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
G/R	0.8251	likely_pathogenic	0.788	pathogenic	-0.359	Destabilizing	1.0	D	0.891	deleterious	D	0.639582803	None	None	I
G/S	0.2733	likely_benign	0.2563	benign	-0.626	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
G/T	0.6591	likely_pathogenic	0.638	pathogenic	-0.709	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/V	0.8834	likely_pathogenic	0.86	pathogenic	-0.312	Destabilizing	1.0	D	0.861	deleterious	D	0.672055494	None	None	I
G/W	0.9273	likely_pathogenic	0.9043	pathogenic	-1.13	Destabilizing	1.0	D	0.863	deleterious	D	0.672257298	None	None	I
G/Y	0.9203	likely_pathogenic	0.9011	pathogenic	-0.772	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I

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.