TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24247	72964;72965;72966	chr2:178573393;178573392;178573391	chr2:179438120;179438119;179438118
N2AB	22606	68041;68042;68043	chr2:178573393;178573392;178573391	chr2:179438120;179438119;179438118
N2A	21679	65260;65261;65262	chr2:178573393;178573392;178573391	chr2:179438120;179438119;179438118
N2B	15182	45769;45770;45771	chr2:178573393;178573392;178573391	chr2:179438120;179438119;179438118
Novex-1	15307	46144;46145;46146	chr2:178573393;178573392;178573391	chr2:179438120;179438119;179438118
Novex-2	15374	46345;46346;46347	chr2:178573393;178573392;178573391	chr2:179438120;179438119;179438118
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-64
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.6291
• 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
D/G	rs1408225629	None	0.822	N	0.429	0.202	0.297718772494	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
D/G	rs1408225629	None	0.822	N	0.429	0.202	0.297718772494	gnomAD-4.0.0	2.89349E-06	None	None	None	None	I	None	0	4.44622E-05	None	0	0	None	0	0	0	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
D/A	0.0905	likely_benign	0.0821	benign	-0.063	Destabilizing	0.698	D	0.457	neutral	N	0.402019777	None	None	I
D/C	0.441	ambiguous	0.3896	ambiguous	0.235	Stabilizing	0.998	D	0.624	neutral	None	None	None	None	I
D/E	0.0944	likely_benign	0.0871	benign	-0.193	Destabilizing	0.006	N	0.08	neutral	N	0.371062152	None	None	I
D/F	0.4297	ambiguous	0.372	ambiguous	-0.232	Destabilizing	0.993	D	0.534	neutral	None	None	None	None	I
D/G	0.1345	likely_benign	0.1137	benign	-0.2	Destabilizing	0.822	D	0.429	neutral	N	0.487254605	None	None	I
D/H	0.1863	likely_benign	0.1722	benign	0.032	Stabilizing	0.97	D	0.424	neutral	N	0.484291657	None	None	I
D/I	0.169	likely_benign	0.1447	benign	0.23	Stabilizing	0.978	D	0.547	neutral	None	None	None	None	I
D/K	0.1882	likely_benign	0.1709	benign	0.554	Stabilizing	0.019	N	0.207	neutral	None	None	None	None	I
D/L	0.204	likely_benign	0.1856	benign	0.23	Stabilizing	0.956	D	0.471	neutral	None	None	None	None	I
D/M	0.3708	ambiguous	0.3267	benign	0.311	Stabilizing	0.998	D	0.53	neutral	None	None	None	None	I
D/N	0.0807	likely_benign	0.0748	benign	0.421	Stabilizing	0.822	D	0.503	neutral	N	0.479635199	None	None	I
D/P	0.5148	ambiguous	0.4169	ambiguous	0.153	Stabilizing	0.978	D	0.393	neutral	None	None	None	None	I
D/Q	0.1846	likely_benign	0.1664	benign	0.407	Stabilizing	0.754	D	0.447	neutral	None	None	None	None	I
D/R	0.243	likely_benign	0.2137	benign	0.629	Stabilizing	0.915	D	0.466	neutral	None	None	None	None	I
D/S	0.0838	likely_benign	0.0754	benign	0.309	Stabilizing	0.86	D	0.446	neutral	None	None	None	None	I
D/T	0.1324	likely_benign	0.1189	benign	0.41	Stabilizing	0.86	D	0.445	neutral	None	None	None	None	I
D/V	0.1022	likely_benign	0.0915	benign	0.153	Stabilizing	0.942	D	0.471	neutral	N	0.453584748	None	None	I
D/W	0.8109	likely_pathogenic	0.7803	pathogenic	-0.192	Destabilizing	0.998	D	0.663	neutral	None	None	None	None	I
D/Y	0.1874	likely_benign	0.1682	benign	-0.005	Destabilizing	0.99	D	0.533	neutral	N	0.47106607	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.