TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22075	66448;66449;66450	chr2:178582146;178582145;178582144	chr2:179446873;179446872;179446871
N2AB	20434	61525;61526;61527	chr2:178582146;178582145;178582144	chr2:179446873;179446872;179446871
N2A	19507	58744;58745;58746	chr2:178582146;178582145;178582144	chr2:179446873;179446872;179446871
N2B	13010	39253;39254;39255	chr2:178582146;178582145;178582144	chr2:179446873;179446872;179446871
Novex-1	13135	39628;39629;39630	chr2:178582146;178582145;178582144	chr2:179446873;179446872;179446871
Novex-2	13202	39829;39830;39831	chr2:178582146;178582145;178582144	chr2:179446873;179446872;179446871
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-48
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2312
• 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
S/G	None	None	0.904	N	0.49	0.274	0.286081765059	gnomAD-4.0.0	1.36935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99649E-07	1.15961E-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
S/A	0.1395	likely_benign	0.1244	benign	-0.711	Destabilizing	0.559	D	0.431	neutral	None	None	None	None	N
S/C	0.172	likely_benign	0.1511	benign	-0.47	Destabilizing	0.997	D	0.683	prob.neutral	N	0.478911018	None	None	N
S/D	0.9161	likely_pathogenic	0.8525	pathogenic	-0.649	Destabilizing	0.926	D	0.57	neutral	None	None	None	None	N
S/E	0.9152	likely_pathogenic	0.8595	pathogenic	-0.547	Destabilizing	0.926	D	0.567	neutral	None	None	None	None	N
S/F	0.4899	ambiguous	0.4048	ambiguous	-0.72	Destabilizing	0.956	D	0.773	deleterious	None	None	None	None	N
S/G	0.2478	likely_benign	0.2033	benign	-1.057	Destabilizing	0.904	D	0.49	neutral	N	0.501189481	None	None	N
S/H	0.7108	likely_pathogenic	0.6168	pathogenic	-1.545	Destabilizing	0.998	D	0.684	prob.neutral	None	None	None	None	N
S/I	0.3944	ambiguous	0.3144	benign	0.128	Stabilizing	0.698	D	0.641	neutral	N	0.491165923	None	None	N
S/K	0.97	likely_pathogenic	0.9444	pathogenic	-0.439	Destabilizing	0.86	D	0.569	neutral	None	None	None	None	N
S/L	0.246	likely_benign	0.1952	benign	0.128	Stabilizing	0.754	D	0.587	neutral	None	None	None	None	N
S/M	0.2978	likely_benign	0.2798	benign	0.197	Stabilizing	0.994	D	0.705	prob.neutral	None	None	None	None	N
S/N	0.4108	ambiguous	0.3309	benign	-0.782	Destabilizing	0.904	D	0.579	neutral	D	0.525103704	None	None	N
S/P	0.9908	likely_pathogenic	0.9836	pathogenic	-0.115	Destabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	N
S/Q	0.8018	likely_pathogenic	0.7295	pathogenic	-0.704	Destabilizing	0.993	D	0.582	neutral	None	None	None	None	N
S/R	0.9505	likely_pathogenic	0.9041	pathogenic	-0.633	Destabilizing	0.97	D	0.699	prob.neutral	N	0.513097199	None	None	N
S/T	0.113	likely_benign	0.1026	benign	-0.609	Destabilizing	0.058	N	0.292	neutral	N	0.460860224	None	None	N
S/V	0.3703	ambiguous	0.3088	benign	-0.115	Destabilizing	0.019	N	0.427	neutral	None	None	None	None	N
S/W	0.7399	likely_pathogenic	0.6467	pathogenic	-0.845	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
S/Y	0.504	ambiguous	0.3959	ambiguous	-0.467	Destabilizing	0.978	D	0.78	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.