TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35130	105613;105614;105615	chr2:178531227;178531226;178531225	chr2:179395954;179395953;179395952
N2AB	33489	100690;100691;100692	chr2:178531227;178531226;178531225	chr2:179395954;179395953;179395952
N2A	32562	97909;97910;97911	chr2:178531227;178531226;178531225	chr2:179395954;179395953;179395952
N2B	26065	78418;78419;78420	chr2:178531227;178531226;178531225	chr2:179395954;179395953;179395952
Novex-1	26190	78793;78794;78795	chr2:178531227;178531226;178531225	chr2:179395954;179395953;179395952
Novex-2	26257	78994;78995;78996	chr2:178531227;178531226;178531225	chr2:179395954;179395953;179395952
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: Ig-164
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.6133
• 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	0.005	N	0.139	0.065	0.3349148499	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.778	likely_pathogenic	0.7965	pathogenic	-0.206	Destabilizing	0.525	D	0.307	neutral	None	None	None	None	I
R/C	0.3971	ambiguous	0.4506	ambiguous	-0.306	Destabilizing	0.998	D	0.355	neutral	None	None	None	None	I
R/D	0.9304	likely_pathogenic	0.9399	pathogenic	0.055	Stabilizing	0.842	D	0.392	neutral	None	None	None	None	I
R/E	0.6931	likely_pathogenic	0.7211	pathogenic	0.143	Stabilizing	0.525	D	0.297	neutral	None	None	None	None	I
R/F	0.8932	likely_pathogenic	0.8915	pathogenic	-0.31	Destabilizing	0.974	D	0.365	neutral	None	None	None	None	I
R/G	0.6598	likely_pathogenic	0.7001	pathogenic	-0.442	Destabilizing	0.801	D	0.377	neutral	N	0.483681775	None	None	I
R/H	0.1977	likely_benign	0.2161	benign	-0.877	Destabilizing	0.991	D	0.405	neutral	None	None	None	None	I
R/I	0.6952	likely_pathogenic	0.6825	pathogenic	0.392	Stabilizing	0.934	D	0.378	neutral	N	0.484188754	None	None	I
R/K	0.1898	likely_benign	0.1859	benign	-0.201	Destabilizing	0.005	N	0.139	neutral	N	0.444629696	None	None	I
R/L	0.6311	likely_pathogenic	0.6548	pathogenic	0.392	Stabilizing	0.728	D	0.362	neutral	None	None	None	None	I
R/M	0.6863	likely_pathogenic	0.6874	pathogenic	-0.046	Destabilizing	0.991	D	0.38	neutral	None	None	None	None	I
R/N	0.8474	likely_pathogenic	0.8499	pathogenic	0.091	Stabilizing	0.842	D	0.333	neutral	None	None	None	None	I
R/P	0.982	likely_pathogenic	0.9873	pathogenic	0.214	Stabilizing	0.974	D	0.382	neutral	None	None	None	None	I
R/Q	0.1865	likely_benign	0.2121	benign	-0.024	Destabilizing	0.842	D	0.368	neutral	None	None	None	None	I
R/S	0.7925	likely_pathogenic	0.8148	pathogenic	-0.415	Destabilizing	0.454	N	0.314	neutral	N	0.469912143	None	None	I
R/T	0.5403	ambiguous	0.5454	ambiguous	-0.172	Destabilizing	0.022	N	0.189	neutral	N	0.460735299	None	None	I
R/V	0.7049	likely_pathogenic	0.7031	pathogenic	0.214	Stabilizing	0.728	D	0.386	neutral	None	None	None	None	I
R/W	0.4927	ambiguous	0.5149	ambiguous	-0.245	Destabilizing	0.998	D	0.377	neutral	None	None	None	None	I
R/Y	0.772	likely_pathogenic	0.7669	pathogenic	0.138	Stabilizing	0.991	D	0.376	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.