TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25994	78205;78206;78207	chr2:178568152;178568151;178568150	chr2:179432879;179432878;179432877
N2AB	24353	73282;73283;73284	chr2:178568152;178568151;178568150	chr2:179432879;179432878;179432877
N2A	23426	70501;70502;70503	chr2:178568152;178568151;178568150	chr2:179432879;179432878;179432877
N2B	16929	51010;51011;51012	chr2:178568152;178568151;178568150	chr2:179432879;179432878;179432877
Novex-1	17054	51385;51386;51387	chr2:178568152;178568151;178568150	chr2:179432879;179432878;179432877
Novex-2	17121	51586;51587;51588	chr2:178568152;178568151;178568150	chr2:179432879;179432878;179432877
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: Fn3-77
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1242
• 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	rs1375270001	-0.436	0.999	D	0.912	0.613	0.915372335003	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
P/L	rs1375270001	-0.436	0.999	D	0.912	0.613	0.915372335003	gnomAD-4.0.0	1.02646E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34936E-05	0	0
P/S	None	None	0.957	D	0.703	0.626	0.614897173524	gnomAD-4.0.0	9.60257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.05E-05	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	0.7964	likely_pathogenic	0.8047	pathogenic	-2.186	Highly Destabilizing	0.992	D	0.799	deleterious	D	0.536573551	None	None	N
P/C	0.9718	likely_pathogenic	0.9628	pathogenic	-2.257	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.27	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
P/E	0.9991	likely_pathogenic	0.9992	pathogenic	-3.113	Highly Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
P/F	0.9997	likely_pathogenic	0.9997	pathogenic	-1.33	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
P/G	0.9923	likely_pathogenic	0.9933	pathogenic	-2.639	Highly Destabilizing	0.997	D	0.861	deleterious	None	None	None	None	N
P/H	0.9989	likely_pathogenic	0.999	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
P/I	0.9909	likely_pathogenic	0.9866	pathogenic	-0.94	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/K	0.9994	likely_pathogenic	0.9995	pathogenic	-1.847	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
P/L	0.9742	likely_pathogenic	0.9712	pathogenic	-0.94	Destabilizing	0.999	D	0.912	deleterious	D	0.575313275	None	None	N
P/M	0.9961	likely_pathogenic	0.9952	pathogenic	-1.268	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/N	0.9995	likely_pathogenic	0.9995	pathogenic	-2.167	Highly Destabilizing	0.999	D	0.898	deleterious	None	None	None	None	N
P/Q	0.9982	likely_pathogenic	0.9982	pathogenic	-2.147	Highly Destabilizing	0.999	D	0.873	deleterious	D	0.565731396	None	None	N
P/R	0.9972	likely_pathogenic	0.9975	pathogenic	-1.511	Destabilizing	0.999	D	0.903	deleterious	D	0.565224417	None	None	N
P/S	0.9838	likely_pathogenic	0.9851	pathogenic	-2.69	Highly Destabilizing	0.957	D	0.703	prob.neutral	D	0.553957017	None	None	N
P/T	0.9743	likely_pathogenic	0.9703	pathogenic	-2.408	Highly Destabilizing	0.999	D	0.832	deleterious	D	0.553196549	None	None	N
P/V	0.9579	likely_pathogenic	0.9358	pathogenic	-1.33	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.742	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9998	pathogenic	-1.443	Destabilizing	1.0	D	0.933	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.