TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18770	56533;56534;56535	chr2:178599593;178599592;178599591	chr2:179464320;179464319;179464318
N2AB	17129	51610;51611;51612	chr2:178599593;178599592;178599591	chr2:179464320;179464319;179464318
N2A	16202	48829;48830;48831	chr2:178599593;178599592;178599591	chr2:179464320;179464319;179464318
N2B	9705	29338;29339;29340	chr2:178599593;178599592;178599591	chr2:179464320;179464319;179464318
Novex-1	9830	29713;29714;29715	chr2:178599593;178599592;178599591	chr2:179464320;179464319;179464318
Novex-2	9897	29914;29915;29916	chr2:178599593;178599592;178599591	chr2:179464320;179464319;179464318
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-116
• Domain position: 83
• Structural Position: 163
• Q(SASA): 0.6169
• 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
L/R	rs1470434078	None	0.997	D	0.656	0.604	0.810797851273	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/R	rs1470434078	None	0.997	D	0.656	0.604	0.810797851273	gnomAD-4.0.0	6.53745E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.22197E-05	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
L/A	0.3197	likely_benign	0.2471	benign	-0.377	Destabilizing	0.953	D	0.611	neutral	None	None	None	None	I
L/C	0.4631	ambiguous	0.3916	ambiguous	-0.741	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	I
L/D	0.8134	likely_pathogenic	0.7326	pathogenic	-0.189	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	I
L/E	0.5837	likely_pathogenic	0.4528	ambiguous	-0.294	Destabilizing	0.998	D	0.663	neutral	None	None	None	None	I
L/F	0.1324	likely_benign	0.1116	benign	-0.644	Destabilizing	0.128	N	0.539	neutral	None	None	None	None	I
L/G	0.6731	likely_pathogenic	0.5868	pathogenic	-0.451	Destabilizing	0.993	D	0.663	neutral	None	None	None	None	I
L/H	0.2338	likely_benign	0.1727	benign	0.074	Stabilizing	0.999	D	0.666	neutral	None	None	None	None	I
L/I	0.1312	likely_benign	0.1167	benign	-0.306	Destabilizing	0.91	D	0.543	neutral	None	None	None	None	I
L/K	0.4282	ambiguous	0.3275	benign	-0.245	Destabilizing	0.998	D	0.648	neutral	None	None	None	None	I
L/M	0.1241	likely_benign	0.1101	benign	-0.512	Destabilizing	0.991	D	0.621	neutral	D	0.532155467	None	None	I
L/N	0.5099	ambiguous	0.4265	ambiguous	-0.083	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	I
L/P	0.9335	likely_pathogenic	0.8906	pathogenic	-0.303	Destabilizing	0.997	D	0.661	neutral	D	0.526348746	None	None	I
L/Q	0.2316	likely_benign	0.175	benign	-0.274	Destabilizing	0.997	D	0.65	neutral	D	0.536542566	None	None	I
L/R	0.3135	likely_benign	0.2342	benign	0.193	Stabilizing	0.997	D	0.656	neutral	D	0.534214337	None	None	I
L/S	0.3763	ambiguous	0.2937	benign	-0.454	Destabilizing	0.993	D	0.644	neutral	None	None	None	None	I
L/T	0.3436	ambiguous	0.2598	benign	-0.462	Destabilizing	0.986	D	0.595	neutral	None	None	None	None	I
L/V	0.1298	likely_benign	0.1116	benign	-0.303	Destabilizing	0.17	N	0.568	neutral	N	0.460599226	None	None	I
L/W	0.3017	likely_benign	0.2284	benign	-0.666	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	I
L/Y	0.3285	likely_benign	0.2565	benign	-0.419	Destabilizing	0.973	D	0.638	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.