TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27197	81814;81815;81816	chr2:178564543;178564542;178564541	chr2:179429270;179429269;179429268
N2AB	25556	76891;76892;76893	chr2:178564543;178564542;178564541	chr2:179429270;179429269;179429268
N2A	24629	74110;74111;74112	chr2:178564543;178564542;178564541	chr2:179429270;179429269;179429268
N2B	18132	54619;54620;54621	chr2:178564543;178564542;178564541	chr2:179429270;179429269;179429268
Novex-1	18257	54994;54995;54996	chr2:178564543;178564542;178564541	chr2:179429270;179429269;179429268
Novex-2	18324	55195;55196;55197	chr2:178564543;178564542;178564541	chr2:179429270;179429269;179429268
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-86
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3106
• 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
D/N	rs1704957831	None	1.0	N	0.722	0.459	0.412587454835	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs1704957831	None	1.0	N	0.722	0.459	0.412587454835	gnomAD-4.0.0	2.0299E-06	None	None	None	None	I	None	1.74727E-05	0	None	0	0	None	0	0	0	4.69704E-05	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
D/A	0.9017	likely_pathogenic	0.8454	pathogenic	-0.604	Destabilizing	1.0	D	0.757	deleterious	N	0.50013501	None	None	I
D/C	0.9727	likely_pathogenic	0.9614	pathogenic	-0.215	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
D/E	0.8828	likely_pathogenic	0.8427	pathogenic	-0.746	Destabilizing	1.0	D	0.443	neutral	N	0.499121052	None	None	I
D/F	0.9892	likely_pathogenic	0.9823	pathogenic	-0.609	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
D/G	0.8841	likely_pathogenic	0.8256	pathogenic	-0.918	Destabilizing	1.0	D	0.73	prob.delet.	D	0.525191478	None	None	I
D/H	0.9383	likely_pathogenic	0.9077	pathogenic	-1.04	Destabilizing	1.0	D	0.699	prob.neutral	D	0.52443101	None	None	I
D/I	0.973	likely_pathogenic	0.9596	pathogenic	0.215	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
D/K	0.982	likely_pathogenic	0.9722	pathogenic	-0.468	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
D/L	0.9654	likely_pathogenic	0.9538	pathogenic	0.215	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
D/M	0.988	likely_pathogenic	0.9813	pathogenic	0.766	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/N	0.2873	likely_benign	0.2636	benign	-0.771	Destabilizing	1.0	D	0.722	prob.delet.	N	0.484753006	None	None	I
D/P	0.9862	likely_pathogenic	0.98	pathogenic	-0.034	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
D/Q	0.9662	likely_pathogenic	0.947	pathogenic	-0.655	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
D/R	0.9762	likely_pathogenic	0.9635	pathogenic	-0.471	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
D/S	0.5676	likely_pathogenic	0.477	ambiguous	-1.026	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
D/T	0.7474	likely_pathogenic	0.663	pathogenic	-0.768	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
D/V	0.9269	likely_pathogenic	0.8913	pathogenic	-0.034	Destabilizing	1.0	D	0.761	deleterious	N	0.51553024	None	None	I
D/W	0.9973	likely_pathogenic	0.9959	pathogenic	-0.553	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
D/Y	0.9199	likely_pathogenic	0.8864	pathogenic	-0.41	Destabilizing	1.0	D	0.71	prob.delet.	D	0.554652039	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.