TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18406	55441;55442;55443	chr2:178602055;178602054;178602053	chr2:179466782;179466781;179466780
N2AB	16765	50518;50519;50520	chr2:178602055;178602054;178602053	chr2:179466782;179466781;179466780
N2A	15838	47737;47738;47739	chr2:178602055;178602054;178602053	chr2:179466782;179466781;179466780
N2B	9341	28246;28247;28248	chr2:178602055;178602054;178602053	chr2:179466782;179466781;179466780
Novex-1	9466	28621;28622;28623	chr2:178602055;178602054;178602053	chr2:179466782;179466781;179466780
Novex-2	9533	28822;28823;28824	chr2:178602055;178602054;178602053	chr2:179466782;179466781;179466780
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-115
• Domain position: 25
• Structural Position: 42
• Q(SASA): 0.5348
• 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
P/S	None	None	1.0	D	0.759	0.623	0.677512986068	gnomAD-4.0.0	1.59328E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8621E-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
P/A	0.9194	likely_pathogenic	0.9018	pathogenic	-0.514	Destabilizing	1.0	D	0.751	deleterious	D	0.544997476	None	None	I
P/C	0.9898	likely_pathogenic	0.9869	pathogenic	-0.459	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/D	0.9776	likely_pathogenic	0.9744	pathogenic	-0.516	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
P/E	0.9696	likely_pathogenic	0.9581	pathogenic	-0.644	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
P/F	0.9946	likely_pathogenic	0.9941	pathogenic	-0.825	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
P/G	0.9562	likely_pathogenic	0.9591	pathogenic	-0.64	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
P/H	0.9759	likely_pathogenic	0.9701	pathogenic	-0.319	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
P/I	0.9599	likely_pathogenic	0.9497	pathogenic	-0.332	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
P/K	0.9762	likely_pathogenic	0.972	pathogenic	-0.494	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/L	0.932	likely_pathogenic	0.9211	pathogenic	-0.332	Destabilizing	1.0	D	0.779	deleterious	D	0.597616388	None	None	I
P/M	0.9752	likely_pathogenic	0.9704	pathogenic	-0.284	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/N	0.9747	likely_pathogenic	0.9694	pathogenic	-0.12	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
P/Q	0.963	likely_pathogenic	0.9544	pathogenic	-0.406	Destabilizing	1.0	D	0.791	deleterious	D	0.544997476	None	None	I
P/R	0.9569	likely_pathogenic	0.9525	pathogenic	0.052	Stabilizing	1.0	D	0.803	deleterious	D	0.597212779	None	None	I
P/S	0.9671	likely_pathogenic	0.9587	pathogenic	-0.422	Destabilizing	1.0	D	0.759	deleterious	D	0.544490497	None	None	I
P/T	0.9242	likely_pathogenic	0.9062	pathogenic	-0.458	Destabilizing	1.0	D	0.757	deleterious	D	0.597212779	None	None	I
P/V	0.9292	likely_pathogenic	0.9126	pathogenic	-0.358	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
P/W	0.9967	likely_pathogenic	0.9962	pathogenic	-0.913	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
P/Y	0.99	likely_pathogenic	0.9883	pathogenic	-0.614	Destabilizing	1.0	D	0.836	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.