TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17693	53302;53303;53304	chr2:178607611;178607610;178607609	chr2:179472338;179472337;179472336
N2AB	16052	48379;48380;48381	chr2:178607611;178607610;178607609	chr2:179472338;179472337;179472336
N2A	15125	45598;45599;45600	chr2:178607611;178607610;178607609	chr2:179472338;179472337;179472336
N2B	8628	26107;26108;26109	chr2:178607611;178607610;178607609	chr2:179472338;179472337;179472336
Novex-1	8753	26482;26483;26484	chr2:178607611;178607610;178607609	chr2:179472338;179472337;179472336
Novex-2	8820	26683;26684;26685	chr2:178607611;178607610;178607609	chr2:179472338;179472337;179472336
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: Ig-113
• Domain position: 17
• Structural Position: 31
• Q(SASA): 0.5138
• 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/L	rs1176166730	-0.027	0.999	N	0.789	0.408	0.680317807054	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
P/L	rs1176166730	-0.027	0.999	N	0.789	0.408	0.680317807054	gnomAD-4.0.0	1.59267E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86069E-06	0	0
P/T	None	None	0.998	N	0.756	0.416	0.531825494424	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2515	likely_benign	0.2497	benign	-0.999	Destabilizing	0.992	D	0.58	neutral	D	0.529381734	None	None	I
P/C	0.8097	likely_pathogenic	0.8093	pathogenic	-0.814	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
P/D	0.8133	likely_pathogenic	0.8233	pathogenic	-0.613	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
P/E	0.68	likely_pathogenic	0.7093	pathogenic	-0.653	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
P/F	0.8457	likely_pathogenic	0.8414	pathogenic	-0.818	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
P/G	0.6736	likely_pathogenic	0.6684	pathogenic	-1.257	Destabilizing	0.997	D	0.683	prob.neutral	None	None	None	None	I
P/H	0.5665	likely_pathogenic	0.5791	pathogenic	-0.743	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/I	0.6739	likely_pathogenic	0.6935	pathogenic	-0.423	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
P/K	0.749	likely_pathogenic	0.7632	pathogenic	-0.884	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	I
P/L	0.3368	likely_benign	0.3415	ambiguous	-0.423	Destabilizing	0.999	D	0.789	deleterious	N	0.515799148	None	None	I
P/M	0.6832	likely_pathogenic	0.6899	pathogenic	-0.436	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/N	0.7148	likely_pathogenic	0.7301	pathogenic	-0.649	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
P/Q	0.5453	ambiguous	0.5561	ambiguous	-0.823	Destabilizing	0.999	D	0.793	deleterious	N	0.487015036	None	None	I
P/R	0.5682	likely_pathogenic	0.5701	pathogenic	-0.375	Destabilizing	0.999	D	0.771	deleterious	N	0.499117542	None	None	I
P/S	0.3681	ambiguous	0.3699	ambiguous	-1.133	Destabilizing	0.957	D	0.447	neutral	N	0.472931018	None	None	I
P/T	0.3073	likely_benign	0.3198	benign	-1.059	Destabilizing	0.998	D	0.756	deleterious	N	0.449515441	None	None	I
P/V	0.5139	ambiguous	0.5293	ambiguous	-0.578	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
P/W	0.9123	likely_pathogenic	0.917	pathogenic	-0.951	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/Y	0.8259	likely_pathogenic	0.8298	pathogenic	-0.658	Destabilizing	1.0	D	0.783	deleterious	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.