TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21256	63991;63992;63993	chr2:178587543;178587542;178587541	chr2:179452270;179452269;179452268
N2AB	19615	59068;59069;59070	chr2:178587543;178587542;178587541	chr2:179452270;179452269;179452268
N2A	18688	56287;56288;56289	chr2:178587543;178587542;178587541	chr2:179452270;179452269;179452268
N2B	12191	36796;36797;36798	chr2:178587543;178587542;178587541	chr2:179452270;179452269;179452268
Novex-1	12316	37171;37172;37173	chr2:178587543;178587542;178587541	chr2:179452270;179452269;179452268
Novex-2	12383	37372;37373;37374	chr2:178587543;178587542;178587541	chr2:179452270;179452269;179452268
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-123
• Domain position: 80
• Structural Position: 168
• Q(SASA): 0.475
• 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
A/T	rs1277491841	-0.638	1.0	N	0.702	0.388	0.500176316166	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	0	2.94E-05	None	0	0	None	0	None	0	0	0
A/T	rs1277491841	-0.638	1.0	N	0.702	0.388	0.500176316166	gnomAD-4.0.0	1.6E-06	None	None	None	None	I	None	0	2.30563E-05	None	0	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
A/C	0.6234	likely_pathogenic	0.6757	pathogenic	-0.677	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
A/D	0.6887	likely_pathogenic	0.7159	pathogenic	-0.439	Destabilizing	1.0	D	0.881	deleterious	N	0.513894993	None	None	I
A/E	0.5912	likely_pathogenic	0.6143	pathogenic	-0.512	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
A/F	0.7035	likely_pathogenic	0.7556	pathogenic	-0.655	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
A/G	0.2886	likely_benign	0.3231	benign	-0.6	Destabilizing	1.0	D	0.555	neutral	N	0.485390068	None	None	I
A/H	0.7306	likely_pathogenic	0.7586	pathogenic	-0.634	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
A/I	0.5799	likely_pathogenic	0.6262	pathogenic	-0.134	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
A/K	0.8099	likely_pathogenic	0.8324	pathogenic	-0.82	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
A/L	0.437	ambiguous	0.4782	ambiguous	-0.134	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
A/M	0.3836	ambiguous	0.4347	ambiguous	-0.298	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
A/N	0.4991	ambiguous	0.5759	pathogenic	-0.527	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
A/P	0.8046	likely_pathogenic	0.8398	pathogenic	-0.191	Destabilizing	1.0	D	0.868	deleterious	N	0.485643558	None	None	I
A/Q	0.5938	likely_pathogenic	0.6351	pathogenic	-0.691	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	I
A/R	0.7379	likely_pathogenic	0.7547	pathogenic	-0.452	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
A/S	0.1495	likely_benign	0.1629	benign	-0.822	Destabilizing	1.0	D	0.553	neutral	N	0.379367496	None	None	I
A/T	0.167	likely_benign	0.1909	benign	-0.8	Destabilizing	1.0	D	0.702	prob.neutral	N	0.399625338	None	None	I
A/V	0.2992	likely_benign	0.3327	benign	-0.191	Destabilizing	1.0	D	0.618	neutral	N	0.499330973	None	None	I
A/W	0.9273	likely_pathogenic	0.9445	pathogenic	-0.926	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
A/Y	0.7435	likely_pathogenic	0.7872	pathogenic	-0.533	Destabilizing	1.0	D	0.887	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.