TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32669	98230;98231;98232	chr2:178540161;178540160;178540159	chr2:179404888;179404887;179404886
N2AB	31028	93307;93308;93309	chr2:178540161;178540160;178540159	chr2:179404888;179404887;179404886
N2A	30101	90526;90527;90528	chr2:178540161;178540160;178540159	chr2:179404888;179404887;179404886
N2B	23604	71035;71036;71037	chr2:178540161;178540160;178540159	chr2:179404888;179404887;179404886
Novex-1	23729	71410;71411;71412	chr2:178540161;178540160;178540159	chr2:179404888;179404887;179404886
Novex-2	23796	71611;71612;71613	chr2:178540161;178540160;178540159	chr2:179404888;179404887;179404886
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-126
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1245
• 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
A/T	None	None	1.0	N	0.697	0.326	0.242244723065	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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
A/C	0.5005	ambiguous	0.4452	ambiguous	-0.899	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
A/D	0.4818	ambiguous	0.4625	ambiguous	-1.662	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
A/E	0.3746	ambiguous	0.3635	ambiguous	-1.581	Destabilizing	1.0	D	0.761	deleterious	N	0.447677496	None	None	N
A/F	0.5663	likely_pathogenic	0.5147	ambiguous	-0.878	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
A/G	0.2275	likely_benign	0.2023	benign	-1.388	Destabilizing	1.0	D	0.533	neutral	N	0.47340266	None	None	N
A/H	0.6748	likely_pathogenic	0.6243	pathogenic	-1.624	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
A/I	0.4334	ambiguous	0.3896	ambiguous	-0.115	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
A/K	0.6985	likely_pathogenic	0.6775	pathogenic	-1.37	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
A/L	0.3209	likely_benign	0.2756	benign	-0.115	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
A/M	0.2824	likely_benign	0.2484	benign	-0.114	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
A/N	0.3977	ambiguous	0.3671	ambiguous	-1.318	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
A/P	0.9312	likely_pathogenic	0.9177	pathogenic	-0.373	Destabilizing	1.0	D	0.755	deleterious	N	0.501616267	None	None	N
A/Q	0.4048	ambiguous	0.3778	ambiguous	-1.321	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
A/R	0.6646	likely_pathogenic	0.6274	pathogenic	-1.142	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
A/S	0.1091	likely_benign	0.1012	benign	-1.709	Destabilizing	1.0	D	0.563	neutral	N	0.474997383	None	None	N
A/T	0.123	likely_benign	0.1132	benign	-1.517	Destabilizing	1.0	D	0.697	prob.neutral	N	0.397184387	None	None	N
A/V	0.2068	likely_benign	0.1913	benign	-0.373	Destabilizing	1.0	D	0.613	neutral	N	0.450005725	None	None	N
A/W	0.8935	likely_pathogenic	0.8563	pathogenic	-1.439	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
A/Y	0.6864	likely_pathogenic	0.6371	pathogenic	-0.932	Destabilizing	1.0	D	0.741	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.