TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31957	96094;96095;96096	chr2:178544360;178544359;178544358	chr2:179409087;179409086;179409085
N2AB	30316	91171;91172;91173	chr2:178544360;178544359;178544358	chr2:179409087;179409086;179409085
N2A	29389	88390;88391;88392	chr2:178544360;178544359;178544358	chr2:179409087;179409086;179409085
N2B	22892	68899;68900;68901	chr2:178544360;178544359;178544358	chr2:179409087;179409086;179409085
Novex-1	23017	69274;69275;69276	chr2:178544360;178544359;178544358	chr2:179409087;179409086;179409085
Novex-2	23084	69475;69476;69477	chr2:178544360;178544359;178544358	chr2:179409087;179409086;179409085
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-121
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4602
• 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
Y/H	rs1302879352	-0.001	0.741	N	0.548	0.303	0.350964488264	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
Y/H	rs1302879352	-0.001	0.741	N	0.548	0.303	0.350964488264	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	2.28655E-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
Y/A	0.2834	likely_benign	0.31	benign	-1.475	Destabilizing	0.081	N	0.514	neutral	None	None	None	None	N
Y/C	0.0826	likely_benign	0.0855	benign	-0.106	Destabilizing	0.001	N	0.446	neutral	N	0.482355791	None	None	N
Y/D	0.1971	likely_benign	0.2117	benign	-0.159	Destabilizing	0.741	D	0.569	neutral	N	0.41389857	None	None	N
Y/E	0.298	likely_benign	0.3136	benign	-0.134	Destabilizing	0.555	D	0.549	neutral	None	None	None	None	N
Y/F	0.08	likely_benign	0.0835	benign	-0.679	Destabilizing	None	N	0.273	neutral	N	0.401662779	None	None	N
Y/G	0.2369	likely_benign	0.2666	benign	-1.729	Destabilizing	0.38	N	0.501	neutral	None	None	None	None	N
Y/H	0.0935	likely_benign	0.0922	benign	-0.444	Destabilizing	0.741	D	0.548	neutral	N	0.425982433	None	None	N
Y/I	0.1847	likely_benign	0.1944	benign	-0.751	Destabilizing	0.081	N	0.497	neutral	None	None	None	None	N
Y/K	0.1939	likely_benign	0.1932	benign	-0.444	Destabilizing	0.555	D	0.545	neutral	None	None	None	None	N
Y/L	0.2161	likely_benign	0.2274	benign	-0.751	Destabilizing	0.001	N	0.298	neutral	None	None	None	None	N
Y/M	0.3042	likely_benign	0.3252	benign	-0.444	Destabilizing	0.38	N	0.522	neutral	None	None	None	None	N
Y/N	0.1067	likely_benign	0.1152	benign	-0.625	Destabilizing	0.484	N	0.561	neutral	N	0.425865003	None	None	N
Y/P	0.8462	likely_pathogenic	0.8566	pathogenic	-0.981	Destabilizing	0.791	D	0.569	neutral	None	None	None	None	N
Y/Q	0.1823	likely_benign	0.183	benign	-0.6	Destabilizing	0.791	D	0.529	neutral	None	None	None	None	N
Y/R	0.1618	likely_benign	0.1569	benign	-0.085	Destabilizing	0.555	D	0.561	neutral	None	None	None	None	N
Y/S	0.1268	likely_benign	0.1361	benign	-1.007	Destabilizing	0.317	N	0.485	neutral	N	0.376014973	None	None	N
Y/T	0.194	likely_benign	0.2086	benign	-0.894	Destabilizing	0.38	N	0.485	neutral	None	None	None	None	N
Y/V	0.154	likely_benign	0.1638	benign	-0.981	Destabilizing	0.081	N	0.516	neutral	None	None	None	None	N
Y/W	0.299	likely_benign	0.3276	benign	-0.557	Destabilizing	0.935	D	0.537	neutral	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.