TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17446	52561;52562;52563	chr2:178608675;178608674;178608673	chr2:179473402;179473401;179473400
N2AB	15805	47638;47639;47640	chr2:178608675;178608674;178608673	chr2:179473402;179473401;179473400
N2A	14878	44857;44858;44859	chr2:178608675;178608674;178608673	chr2:179473402;179473401;179473400
N2B	8381	25366;25367;25368	chr2:178608675;178608674;178608673	chr2:179473402;179473401;179473400
Novex-1	8506	25741;25742;25743	chr2:178608675;178608674;178608673	chr2:179473402;179473401;179473400
Novex-2	8573	25942;25943;25944	chr2:178608675;178608674;178608673	chr2:179473402;179473401;179473400
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-14
• Domain position: 78
• Structural Position: 109
• Q(SASA): 0.2532
• 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
R/K	None	None	None	N	0.164	0.112	0.234412748748	gnomAD-4.0.0	4.10947E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.40011E-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
R/A	0.5267	ambiguous	0.4808	ambiguous	-1.394	Destabilizing	0.016	N	0.362	neutral	None	None	None	None	I
R/C	0.1949	likely_benign	0.1626	benign	-1.634	Destabilizing	0.901	D	0.703	prob.neutral	None	None	None	None	I
R/D	0.9146	likely_pathogenic	0.9033	pathogenic	-0.855	Destabilizing	0.148	N	0.597	neutral	None	None	None	None	I
R/E	0.621	likely_pathogenic	0.5906	pathogenic	-0.7	Destabilizing	0.08	N	0.429	neutral	None	None	None	None	I
R/F	0.5894	likely_pathogenic	0.512	ambiguous	-1.049	Destabilizing	0.001	N	0.485	neutral	None	None	None	None	I
R/G	0.5301	ambiguous	0.4737	ambiguous	-1.71	Destabilizing	0.116	N	0.473	neutral	N	0.487310674	None	None	I
R/H	0.1622	likely_benign	0.1333	benign	-1.644	Destabilizing	0.749	D	0.529	neutral	None	None	None	None	I
R/I	0.3736	ambiguous	0.335	benign	-0.516	Destabilizing	0.061	N	0.524	neutral	N	0.485985168	None	None	I
R/K	0.1539	likely_benign	0.1304	benign	-1.488	Destabilizing	None	N	0.164	neutral	N	0.469148847	None	None	I
R/L	0.3534	ambiguous	0.3063	benign	-0.516	Destabilizing	0.036	N	0.436	neutral	None	None	None	None	I
R/M	0.2996	likely_benign	0.2558	benign	-0.889	Destabilizing	0.749	D	0.651	neutral	None	None	None	None	I
R/N	0.7647	likely_pathogenic	0.7177	pathogenic	-1.161	Destabilizing	0.148	N	0.526	neutral	None	None	None	None	I
R/P	0.9882	likely_pathogenic	0.988	pathogenic	-0.792	Destabilizing	0.46	N	0.68	prob.neutral	None	None	None	None	I
R/Q	0.1472	likely_benign	0.1305	benign	-1.212	Destabilizing	0.174	N	0.589	neutral	None	None	None	None	I
R/S	0.549	ambiguous	0.4828	ambiguous	-1.932	Destabilizing	0.005	N	0.267	neutral	N	0.427977015	None	None	I
R/T	0.2867	likely_benign	0.236	benign	-1.59	Destabilizing	0.001	N	0.257	neutral	N	0.443541113	None	None	I
R/V	0.4098	ambiguous	0.3731	ambiguous	-0.792	Destabilizing	0.001	N	0.454	neutral	None	None	None	None	I
R/W	0.2674	likely_benign	0.227	benign	-0.659	Destabilizing	0.972	D	0.705	prob.neutral	None	None	None	None	I
R/Y	0.503	ambiguous	0.4358	ambiguous	-0.373	Destabilizing	0.174	N	0.671	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.