TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16551	49876;49877;49878	chr2:178613070;178613069;178613068	chr2:179477797;179477796;179477795
N2AB	14910	44953;44954;44955	chr2:178613070;178613069;178613068	chr2:179477797;179477796;179477795
N2A	13983	42172;42173;42174	chr2:178613070;178613069;178613068	chr2:179477797;179477796;179477795
N2B	7486	22681;22682;22683	chr2:178613070;178613069;178613068	chr2:179477797;179477796;179477795
Novex-1	7611	23056;23057;23058	chr2:178613070;178613069;178613068	chr2:179477797;179477796;179477795
Novex-2	7678	23257;23258;23259	chr2:178613070;178613069;178613068	chr2:179477797;179477796;179477795
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: Fn3-8
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5999
• 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	rs1462000296	-0.167	1.0	N	0.827	0.373	0.535152128566	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
P/L	rs1462000296	-0.167	1.0	N	0.827	0.373	0.535152128566	gnomAD-4.0.0	1.59417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86285E-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	0.1824	likely_benign	0.19	benign	-0.622	Destabilizing	0.999	D	0.771	deleterious	D	0.561047806	None	None	N
P/C	0.8349	likely_pathogenic	0.8367	pathogenic	-0.586	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/D	0.9446	likely_pathogenic	0.9609	pathogenic	-0.372	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/E	0.7721	likely_pathogenic	0.8036	pathogenic	-0.496	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
P/F	0.8877	likely_pathogenic	0.9109	pathogenic	-0.983	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/G	0.8341	likely_pathogenic	0.8654	pathogenic	-0.748	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/H	0.6295	likely_pathogenic	0.704	pathogenic	-0.349	Destabilizing	1.0	D	0.833	deleterious	D	0.606959467	None	None	N
P/I	0.577	likely_pathogenic	0.544	ambiguous	-0.441	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/K	0.5997	likely_pathogenic	0.6746	pathogenic	-0.31	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/L	0.3179	likely_benign	0.352	ambiguous	-0.441	Destabilizing	1.0	D	0.827	deleterious	N	0.451461877	None	None	N
P/M	0.6728	likely_pathogenic	0.6716	pathogenic	-0.237	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/N	0.8669	likely_pathogenic	0.8847	pathogenic	-0.044	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/Q	0.5058	ambiguous	0.5384	ambiguous	-0.363	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/R	0.4738	ambiguous	0.5672	pathogenic	0.22	Stabilizing	1.0	D	0.853	deleterious	D	0.562813571	None	None	N
P/S	0.4489	ambiguous	0.494	ambiguous	-0.436	Destabilizing	1.0	D	0.811	deleterious	D	0.566061274	None	None	N
P/T	0.3593	ambiguous	0.3524	ambiguous	-0.464	Destabilizing	1.0	D	0.799	deleterious	D	0.644315625	None	None	N
P/V	0.4451	ambiguous	0.4133	ambiguous	-0.467	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
P/W	0.9676	likely_pathogenic	0.9784	pathogenic	-1.02	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
P/Y	0.8855	likely_pathogenic	0.9196	pathogenic	-0.69	Destabilizing	1.0	D	0.847	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.