TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27056	81391;81392;81393	chr2:178564966;178564965;178564964	chr2:179429693;179429692;179429691
N2AB	25415	76468;76469;76470	chr2:178564966;178564965;178564964	chr2:179429693;179429692;179429691
N2A	24488	73687;73688;73689	chr2:178564966;178564965;178564964	chr2:179429693;179429692;179429691
N2B	17991	54196;54197;54198	chr2:178564966;178564965;178564964	chr2:179429693;179429692;179429691
Novex-1	18116	54571;54572;54573	chr2:178564966;178564965;178564964	chr2:179429693;179429692;179429691
Novex-2	18183	54772;54773;54774	chr2:178564966;178564965;178564964	chr2:179429693;179429692;179429691
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-84
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.0814
• 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
S/N	None	None	0.722	D	0.758	0.394	0.255777322467	gnomAD-4.0.0	6.85037E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00105E-07	0	0
S/R	None	None	0.901	D	0.782	0.374	0.243398259712	gnomAD-4.0.0	6.84945E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00028E-07	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
S/A	0.4351	ambiguous	0.3805	ambiguous	-0.845	Destabilizing	0.011	N	0.431	neutral	None	None	None	None	N
S/C	0.7522	likely_pathogenic	0.696	pathogenic	-0.635	Destabilizing	0.986	D	0.756	deleterious	D	0.547147302	None	None	N
S/D	0.9781	likely_pathogenic	0.9808	pathogenic	-0.948	Destabilizing	0.775	D	0.765	deleterious	None	None	None	None	N
S/E	0.9935	likely_pathogenic	0.9935	pathogenic	-0.829	Destabilizing	0.775	D	0.758	deleterious	None	None	None	None	N
S/F	0.9931	likely_pathogenic	0.9912	pathogenic	-0.587	Destabilizing	0.961	D	0.829	deleterious	None	None	None	None	N
S/G	0.0946	likely_benign	0.1066	benign	-1.203	Destabilizing	0.008	N	0.451	neutral	N	0.460809004	None	None	N
S/H	0.9862	likely_pathogenic	0.9851	pathogenic	-1.485	Destabilizing	0.996	D	0.756	deleterious	None	None	None	None	N
S/I	0.9905	likely_pathogenic	0.9875	pathogenic	0.042	Stabilizing	0.901	D	0.853	deleterious	D	0.546640322	None	None	N
S/K	0.9983	likely_pathogenic	0.9985	pathogenic	-0.663	Destabilizing	0.775	D	0.755	deleterious	None	None	None	None	N
S/L	0.956	likely_pathogenic	0.9389	pathogenic	0.042	Stabilizing	0.633	D	0.823	deleterious	None	None	None	None	N
S/M	0.9714	likely_pathogenic	0.9538	pathogenic	0.049	Stabilizing	0.996	D	0.757	deleterious	None	None	None	None	N
S/N	0.9334	likely_pathogenic	0.9235	pathogenic	-0.998	Destabilizing	0.722	D	0.758	deleterious	D	0.546386833	None	None	N
S/P	0.9938	likely_pathogenic	0.9925	pathogenic	-0.219	Destabilizing	0.961	D	0.785	deleterious	None	None	None	None	N
S/Q	0.9926	likely_pathogenic	0.9919	pathogenic	-0.92	Destabilizing	0.961	D	0.749	deleterious	None	None	None	None	N
S/R	0.9972	likely_pathogenic	0.9974	pathogenic	-0.775	Destabilizing	0.901	D	0.782	deleterious	D	0.545372875	None	None	N
S/T	0.7075	likely_pathogenic	0.6439	pathogenic	-0.833	Destabilizing	0.722	D	0.725	prob.delet.	D	0.523256148	None	None	N
S/V	0.9835	likely_pathogenic	0.977	pathogenic	-0.219	Destabilizing	0.858	D	0.824	deleterious	None	None	None	None	N
S/W	0.9935	likely_pathogenic	0.9925	pathogenic	-0.703	Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
S/Y	0.984	likely_pathogenic	0.9802	pathogenic	-0.362	Destabilizing	0.987	D	0.85	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.