TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23535	70828;70829;70830	chr2:178575529;178575528;178575527	chr2:179440256;179440255;179440254
N2AB	21894	65905;65906;65907	chr2:178575529;178575528;178575527	chr2:179440256;179440255;179440254
N2A	20967	63124;63125;63126	chr2:178575529;178575528;178575527	chr2:179440256;179440255;179440254
N2B	14470	43633;43634;43635	chr2:178575529;178575528;178575527	chr2:179440256;179440255;179440254
Novex-1	14595	44008;44009;44010	chr2:178575529;178575528;178575527	chr2:179440256;179440255;179440254
Novex-2	14662	44209;44210;44211	chr2:178575529;178575528;178575527	chr2:179440256;179440255;179440254
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: Fn3-59
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1981
• 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
P/L	None	None	1.0	D	0.838	0.481	0.663460038712	gnomAD-4.0.0	1.59147E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	0	0
P/R	None	None	1.0	N	0.873	0.474	0.501685917333	gnomAD-4.0.0	1.59147E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-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
P/A	0.0922	likely_benign	0.0913	benign	-1.652	Destabilizing	0.731	D	0.449	neutral	N	0.493329641	None	None	N
P/C	0.5736	likely_pathogenic	0.6071	pathogenic	-1.262	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/D	0.912	likely_pathogenic	0.9079	pathogenic	-2.293	Highly Destabilizing	0.998	D	0.824	deleterious	None	None	None	None	N
P/E	0.6279	likely_pathogenic	0.6173	pathogenic	-2.301	Highly Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
P/F	0.7463	likely_pathogenic	0.7578	pathogenic	-1.402	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/G	0.6444	likely_pathogenic	0.6416	pathogenic	-1.948	Destabilizing	0.997	D	0.785	deleterious	None	None	None	None	N
P/H	0.509	ambiguous	0.5278	ambiguous	-1.466	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/I	0.4254	ambiguous	0.4467	ambiguous	-0.926	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/K	0.7114	likely_pathogenic	0.7081	pathogenic	-1.352	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
P/L	0.2777	likely_benign	0.2757	benign	-0.926	Destabilizing	1.0	D	0.838	deleterious	D	0.531547807	None	None	N
P/M	0.4801	ambiguous	0.4834	ambiguous	-0.714	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/N	0.7791	likely_pathogenic	0.7905	pathogenic	-1.254	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/Q	0.391	ambiguous	0.3856	ambiguous	-1.505	Destabilizing	1.0	D	0.829	deleterious	N	0.503275335	None	None	N
P/R	0.5482	ambiguous	0.5482	ambiguous	-0.786	Destabilizing	1.0	D	0.873	deleterious	N	0.507567749	None	None	N
P/S	0.2071	likely_benign	0.2228	benign	-1.669	Destabilizing	0.997	D	0.785	deleterious	N	0.490842619	None	None	N
P/T	0.2494	likely_benign	0.2551	benign	-1.584	Destabilizing	0.999	D	0.815	deleterious	N	0.506353208	None	None	N
P/V	0.2742	likely_benign	0.2883	benign	-1.137	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/W	0.9025	likely_pathogenic	0.9181	pathogenic	-1.605	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/Y	0.7792	likely_pathogenic	0.7842	pathogenic	-1.318	Destabilizing	1.0	D	0.883	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.