TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35486	106681;106682;106683	chr2:178530035;178530034;178530033	chr2:179394762;179394761;179394760
N2AB	33845	101758;101759;101760	chr2:178530035;178530034;178530033	chr2:179394762;179394761;179394760
N2A	32918	98977;98978;98979	chr2:178530035;178530034;178530033	chr2:179394762;179394761;179394760
N2B	26421	79486;79487;79488	chr2:178530035;178530034;178530033	chr2:179394762;179394761;179394760
Novex-1	26546	79861;79862;79863	chr2:178530035;178530034;178530033	chr2:179394762;179394761;179394760
Novex-2	26613	80062;80063;80064	chr2:178530035;178530034;178530033	chr2:179394762;179394761;179394760
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-166
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1026
• 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
D/E	None	None	0.992	D	0.636	0.652	0.585473498874	gnomAD-4.0.0	6.85896E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00161E-07	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
D/A	0.6269	likely_pathogenic	0.6625	pathogenic	-0.133	Destabilizing	0.999	D	0.865	deleterious	D	0.615084073	None	None	N
D/C	0.9201	likely_pathogenic	0.9215	pathogenic	0.024	Stabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
D/E	0.6011	likely_pathogenic	0.6158	pathogenic	-0.882	Destabilizing	0.992	D	0.636	neutral	D	0.595067911	None	None	N
D/F	0.9212	likely_pathogenic	0.9332	pathogenic	0.302	Stabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
D/G	0.6871	likely_pathogenic	0.7133	pathogenic	-0.57	Destabilizing	0.997	D	0.787	deleterious	D	0.631537403	None	None	N
D/H	0.7599	likely_pathogenic	0.763	pathogenic	-0.016	Destabilizing	1.0	D	0.874	deleterious	D	0.584841948	None	None	N
D/I	0.8394	likely_pathogenic	0.8634	pathogenic	1.049	Stabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
D/K	0.9113	likely_pathogenic	0.9098	pathogenic	0.105	Stabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
D/L	0.8707	likely_pathogenic	0.8894	pathogenic	1.049	Stabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
D/M	0.9516	likely_pathogenic	0.9582	pathogenic	1.579	Stabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
D/N	0.3449	ambiguous	0.3516	ambiguous	-0.737	Destabilizing	0.997	D	0.744	deleterious	D	0.592342656	None	None	N
D/P	0.9773	likely_pathogenic	0.9789	pathogenic	0.682	Stabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
D/Q	0.8673	likely_pathogenic	0.8671	pathogenic	-0.44	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
D/R	0.9193	likely_pathogenic	0.9189	pathogenic	0.06	Stabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
D/S	0.4312	ambiguous	0.4546	ambiguous	-1.02	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
D/T	0.7548	likely_pathogenic	0.7808	pathogenic	-0.599	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
D/V	0.6666	likely_pathogenic	0.7127	pathogenic	0.682	Stabilizing	0.999	D	0.887	deleterious	D	0.647960372	None	None	N
D/W	0.9882	likely_pathogenic	0.9897	pathogenic	0.398	Stabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
D/Y	0.6677	likely_pathogenic	0.6872	pathogenic	0.591	Stabilizing	1.0	D	0.899	deleterious	D	0.647758568	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.