TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16374	49345;49346;49347	chr2:178614277;178614276;178614275	chr2:179479004;179479003;179479002
N2AB	14733	44422;44423;44424	chr2:178614277;178614276;178614275	chr2:179479004;179479003;179479002
N2A	13806	41641;41642;41643	chr2:178614277;178614276;178614275	chr2:179479004;179479003;179479002
N2B	7309	22150;22151;22152	chr2:178614277;178614276;178614275	chr2:179479004;179479003;179479002
Novex-1	7434	22525;22526;22527	chr2:178614277;178614276;178614275	chr2:179479004;179479003;179479002
Novex-2	7501	22726;22727;22728	chr2:178614277;178614276;178614275	chr2:179479004;179479003;179479002
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: Fn3-6
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5008
• 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/S	None	None	1.0	D	0.864	0.462	0.452737964553	gnomAD-4.0.0	1.59331E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-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	0.1061	likely_benign	0.0938	benign	-1.664	Destabilizing	1.0	D	0.819	deleterious	N	0.487440911	None	None	N
P/C	0.6986	likely_pathogenic	0.6414	pathogenic	-1.097	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/D	0.8536	likely_pathogenic	0.8136	pathogenic	-1.772	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/E	0.5051	ambiguous	0.4377	ambiguous	-1.701	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/F	0.7537	likely_pathogenic	0.6882	pathogenic	-1.197	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/G	0.6986	likely_pathogenic	0.61	pathogenic	-2.04	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/H	0.4308	ambiguous	0.3891	ambiguous	-1.55	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/I	0.3785	ambiguous	0.3404	ambiguous	-0.694	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/K	0.4796	ambiguous	0.4088	ambiguous	-1.471	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/L	0.1923	likely_benign	0.1661	benign	-0.694	Destabilizing	1.0	D	0.879	deleterious	D	0.650200772	None	None	N
P/M	0.4205	ambiguous	0.3796	ambiguous	-0.571	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/N	0.7049	likely_pathogenic	0.6542	pathogenic	-1.393	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/Q	0.2997	likely_benign	0.2594	benign	-1.464	Destabilizing	1.0	D	0.893	deleterious	D	0.538981682	None	None	N
P/R	0.413	ambiguous	0.3597	ambiguous	-1.013	Destabilizing	1.0	D	0.895	deleterious	D	0.599252272	None	None	N
P/S	0.2854	likely_benign	0.2396	benign	-1.896	Destabilizing	1.0	D	0.864	deleterious	D	0.584605025	None	None	N
P/T	0.2262	likely_benign	0.2055	benign	-1.7	Destabilizing	1.0	D	0.869	deleterious	D	0.618258752	None	None	N
P/V	0.2812	likely_benign	0.254	benign	-0.985	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/W	0.9235	likely_pathogenic	0.8968	pathogenic	-1.463	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/Y	0.7627	likely_pathogenic	0.697	pathogenic	-1.147	Destabilizing	1.0	D	0.881	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.