TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2107	6544;6545;6546	chr2:178775545;178775544;178775543	chr2:179640272;179640271;179640270
N2AB	2107	6544;6545;6546	chr2:178775545;178775544;178775543	chr2:179640272;179640271;179640270
N2A	2107	6544;6545;6546	chr2:178775545;178775544;178775543	chr2:179640272;179640271;179640270
N2B	2061	6406;6407;6408	chr2:178775545;178775544;178775543	chr2:179640272;179640271;179640270
Novex-1	2061	6406;6407;6408	chr2:178775545;178775544;178775543	chr2:179640272;179640271;179640270
Novex-2	2061	6406;6407;6408	chr2:178775545;178775544;178775543	chr2:179640272;179640271;179640270
Novex-3	2107	6544;6545;6546	chr2:178775545;178775544;178775543	chr2:179640272;179640271;179640270

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-10
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1425
• 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/R	None	None	1.0	D	0.843	0.828	0.692713709614	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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	0.7242	likely_pathogenic	0.7099	pathogenic	-1.814	Destabilizing	1.0	D	0.777	deleterious	D	0.670822469	None	None	N
P/C	0.9839	likely_pathogenic	0.9801	pathogenic	-1.351	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9993	pathogenic	-2.487	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/E	0.9978	likely_pathogenic	0.9977	pathogenic	-2.436	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/F	0.9985	likely_pathogenic	0.9982	pathogenic	-1.34	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
P/G	0.9848	likely_pathogenic	0.9856	pathogenic	-2.187	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/H	0.9972	likely_pathogenic	0.9968	pathogenic	-1.867	Destabilizing	1.0	D	0.8	deleterious	D	0.76952242	None	None	N
P/I	0.9447	likely_pathogenic	0.9304	pathogenic	-0.843	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/K	0.9985	likely_pathogenic	0.9985	pathogenic	-1.518	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/L	0.9329	likely_pathogenic	0.9288	pathogenic	-0.843	Destabilizing	1.0	D	0.832	deleterious	D	0.659909943	None	None	N
P/M	0.9813	likely_pathogenic	0.9791	pathogenic	-0.682	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/N	0.998	likely_pathogenic	0.998	pathogenic	-1.477	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/Q	0.9958	likely_pathogenic	0.9955	pathogenic	-1.606	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/R	0.9959	likely_pathogenic	0.9957	pathogenic	-1.071	Destabilizing	1.0	D	0.843	deleterious	D	0.747149246	None	None	N
P/S	0.9721	likely_pathogenic	0.97	pathogenic	-1.938	Destabilizing	1.0	D	0.833	deleterious	D	0.802234167	None	None	N
P/T	0.9257	likely_pathogenic	0.9211	pathogenic	-1.783	Destabilizing	1.0	D	0.841	deleterious	D	0.746157966	None	None	N
P/V	0.8827	likely_pathogenic	0.8618	pathogenic	-1.137	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.689	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
P/Y	0.9993	likely_pathogenic	0.9991	pathogenic	-1.385	Destabilizing	1.0	D	0.823	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.