TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29147	87664;87665;87666	chr2:178557915;178557914;178557913	chr2:179422642;179422641;179422640
N2AB	27506	82741;82742;82743	chr2:178557915;178557914;178557913	chr2:179422642;179422641;179422640
N2A	26579	79960;79961;79962	chr2:178557915;178557914;178557913	chr2:179422642;179422641;179422640
N2B	20082	60469;60470;60471	chr2:178557915;178557914;178557913	chr2:179422642;179422641;179422640
Novex-1	20207	60844;60845;60846	chr2:178557915;178557914;178557913	chr2:179422642;179422641;179422640
Novex-2	20274	61045;61046;61047	chr2:178557915;178557914;178557913	chr2:179422642;179422641;179422640
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-100
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.2482
• 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
I/M	None	None	0.267	N	0.361	0.15	0.262175524916	gnomAD-4.0.0	6.84382E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99428E-07	0	0
I/T	rs1395690668	None	0.051	N	0.309	0.258	0.675682906761	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs1395690668	None	0.051	N	0.309	0.258	0.675682906761	gnomAD-4.0.0	4.33876E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.08538E-06	0	1.60102E-05

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
I/A	0.5053	ambiguous	0.5118	ambiguous	-1.663	Destabilizing	0.525	D	0.434	neutral	None	None	None	None	I
I/C	0.6472	likely_pathogenic	0.6592	pathogenic	-1.237	Destabilizing	0.998	D	0.604	neutral	None	None	None	None	I
I/D	0.9312	likely_pathogenic	0.9211	pathogenic	-0.686	Destabilizing	0.949	D	0.683	prob.neutral	None	None	None	None	I
I/E	0.8637	likely_pathogenic	0.8459	pathogenic	-0.614	Destabilizing	0.949	D	0.691	prob.neutral	None	None	None	None	I
I/F	0.1216	likely_benign	0.125	benign	-0.942	Destabilizing	0.801	D	0.593	neutral	N	0.458662494	None	None	I
I/G	0.85	likely_pathogenic	0.856	pathogenic	-2.056	Highly Destabilizing	0.842	D	0.695	prob.neutral	None	None	None	None	I
I/H	0.7753	likely_pathogenic	0.7681	pathogenic	-1.243	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	I
I/K	0.755	likely_pathogenic	0.7331	pathogenic	-1.159	Destabilizing	0.842	D	0.696	prob.neutral	None	None	None	None	I
I/L	0.0974	likely_benign	0.1041	benign	-0.629	Destabilizing	0.002	N	0.151	neutral	N	0.476421535	None	None	I
I/M	0.1082	likely_benign	0.1102	benign	-0.651	Destabilizing	0.267	N	0.361	neutral	N	0.521868611	None	None	I
I/N	0.6601	likely_pathogenic	0.6327	pathogenic	-1.091	Destabilizing	0.934	D	0.675	neutral	N	0.503871219	None	None	I
I/P	0.7019	likely_pathogenic	0.7524	pathogenic	-0.942	Destabilizing	0.974	D	0.667	neutral	None	None	None	None	I
I/Q	0.7414	likely_pathogenic	0.7219	pathogenic	-1.116	Destabilizing	0.974	D	0.667	neutral	None	None	None	None	I
I/R	0.6762	likely_pathogenic	0.6669	pathogenic	-0.753	Destabilizing	0.974	D	0.673	neutral	None	None	None	None	I
I/S	0.5972	likely_pathogenic	0.5875	pathogenic	-1.841	Destabilizing	0.669	D	0.611	neutral	N	0.496527385	None	None	I
I/T	0.4645	ambiguous	0.4514	ambiguous	-1.629	Destabilizing	0.051	N	0.309	neutral	N	0.472587007	None	None	I
I/V	0.0821	likely_benign	0.0819	benign	-0.942	Destabilizing	0.267	N	0.367	neutral	N	0.41629301	None	None	I
I/W	0.7886	likely_pathogenic	0.799	pathogenic	-1.036	Destabilizing	0.998	D	0.646	neutral	None	None	None	None	I
I/Y	0.566	likely_pathogenic	0.572	pathogenic	-0.801	Destabilizing	0.974	D	0.616	neutral	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.