TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9046	27361;27362;27363	chr2:178712889;178712888;178712887	chr2:179577616;179577615;179577614
N2AB	8729	26410;26411;26412	chr2:178712889;178712888;178712887	chr2:179577616;179577615;179577614
N2A	7802	23629;23630;23631	chr2:178712889;178712888;178712887	chr2:179577616;179577615;179577614
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-76
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.3568
• 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	rs772800519	-0.592	0.136	N	0.16	0.4	0.317084106153	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	0	2.03678E-04	None	0	0	None	0	None	0	0	0
P/S	rs772800519	-0.592	0.136	N	0.16	0.4	0.317084106153	gnomAD-4.0.0	6.84321E-06	None	None	None	None	I	None	0	2.01468E-04	None	3.82878E-05	0	None	0	0	0	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	0.0807	likely_benign	0.0901	benign	-0.48	Destabilizing	0.022	N	0.167	neutral	N	0.510105639	None	None	I
P/C	0.5899	likely_pathogenic	0.6848	pathogenic	-0.744	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	I
P/D	0.5873	likely_pathogenic	0.6511	pathogenic	-0.395	Destabilizing	0.016	N	0.16	neutral	None	None	None	None	I
P/E	0.3258	likely_benign	0.36	ambiguous	-0.485	Destabilizing	0.728	D	0.381	neutral	None	None	None	None	I
P/F	0.4304	ambiguous	0.5061	ambiguous	-0.667	Destabilizing	0.949	D	0.578	neutral	None	None	None	None	I
P/G	0.3976	ambiguous	0.4748	ambiguous	-0.598	Destabilizing	0.688	D	0.396	neutral	None	None	None	None	I
P/H	0.2126	likely_benign	0.258	benign	-0.053	Destabilizing	0.997	D	0.509	neutral	D	0.607367303	None	None	I
P/I	0.3332	likely_benign	0.3884	ambiguous	-0.302	Destabilizing	0.728	D	0.561	neutral	None	None	None	None	I
P/K	0.2887	likely_benign	0.3496	ambiguous	-0.492	Destabilizing	0.842	D	0.439	neutral	None	None	None	None	I
P/L	0.1162	likely_benign	0.135	benign	-0.302	Destabilizing	0.012	N	0.211	neutral	D	0.578346722	None	None	I
P/M	0.3036	likely_benign	0.3512	ambiguous	-0.587	Destabilizing	0.949	D	0.52	neutral	None	None	None	None	I
P/N	0.4597	ambiguous	0.5297	ambiguous	-0.326	Destabilizing	0.842	D	0.528	neutral	None	None	None	None	I
P/Q	0.1686	likely_benign	0.1993	benign	-0.519	Destabilizing	0.974	D	0.521	neutral	None	None	None	None	I
P/R	0.1799	likely_benign	0.2232	benign	-0.006	Destabilizing	0.966	D	0.547	neutral	D	0.613696469	None	None	I
P/S	0.1263	likely_benign	0.1458	benign	-0.654	Destabilizing	0.136	N	0.16	neutral	N	0.521942471	None	None	I
P/T	0.1337	likely_benign	0.1546	benign	-0.645	Destabilizing	0.669	D	0.377	neutral	D	0.567263539	None	None	I
P/V	0.222	likely_benign	0.2624	benign	-0.33	Destabilizing	0.728	D	0.443	neutral	None	None	None	None	I
P/W	0.6372	likely_pathogenic	0.7138	pathogenic	-0.748	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	I
P/Y	0.4144	ambiguous	0.4753	ambiguous	-0.465	Destabilizing	0.974	D	0.569	neutral	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.