TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34334	103225;103226;103227	chr2:178533615;178533614;178533613	chr2:179398342;179398341;179398340
N2AB	32693	98302;98303;98304	chr2:178533615;178533614;178533613	chr2:179398342;179398341;179398340
N2A	31766	95521;95522;95523	chr2:178533615;178533614;178533613	chr2:179398342;179398341;179398340
N2B	25269	76030;76031;76032	chr2:178533615;178533614;178533613	chr2:179398342;179398341;179398340
Novex-1	25394	76405;76406;76407	chr2:178533615;178533614;178533613	chr2:179398342;179398341;179398340
Novex-2	25461	76606;76607;76608	chr2:178533615;178533614;178533613	chr2:179398342;179398341;179398340
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-161
• Domain position: 77
• Structural Position: 157
• Q(SASA): 0.177
• 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
V/E	None	None	0.549	N	0.655	0.399	0.759655384941	gnomAD-4.0.0	4.77297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.573E-06	0	0
V/G	rs760991295	-2.527	0.004	N	0.553	0.374	0.737734676174	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
V/G	rs760991295	-2.527	0.004	N	0.553	0.374	0.737734676174	gnomAD-4.0.0	1.59099E-06	None	None	None	None	N	None	0	0	None	0	2.77269E-05	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
V/A	0.304	likely_benign	0.3012	benign	-1.723	Destabilizing	0.002	N	0.267	neutral	D	0.530923316	None	None	N
V/C	0.8381	likely_pathogenic	0.8653	pathogenic	-1.244	Destabilizing	0.992	D	0.635	neutral	None	None	None	None	N
V/D	0.7656	likely_pathogenic	0.763	pathogenic	-1.922	Destabilizing	0.92	D	0.697	prob.neutral	None	None	None	None	N
V/E	0.4711	ambiguous	0.4963	ambiguous	-1.758	Destabilizing	0.549	D	0.655	neutral	N	0.501408486	None	None	N
V/F	0.2541	likely_benign	0.2922	benign	-1.012	Destabilizing	0.739	D	0.653	neutral	None	None	None	None	N
V/G	0.6111	likely_pathogenic	0.6612	pathogenic	-2.199	Highly Destabilizing	0.004	N	0.553	neutral	N	0.508306943	None	None	N
V/H	0.6661	likely_pathogenic	0.7019	pathogenic	-1.915	Destabilizing	0.992	D	0.689	prob.neutral	None	None	None	None	N
V/I	0.0794	likely_benign	0.0809	benign	-0.43	Destabilizing	0.25	N	0.553	neutral	None	None	None	None	N
V/K	0.4182	ambiguous	0.4562	ambiguous	-1.241	Destabilizing	0.617	D	0.645	neutral	None	None	None	None	N
V/L	0.1822	likely_benign	0.2492	benign	-0.43	Destabilizing	0.002	N	0.263	neutral	N	0.481612003	None	None	N
V/M	0.1296	likely_benign	0.1774	benign	-0.524	Destabilizing	0.045	N	0.391	neutral	N	0.502333992	None	None	N
V/N	0.6058	likely_pathogenic	0.6301	pathogenic	-1.391	Destabilizing	0.92	D	0.697	prob.neutral	None	None	None	None	N
V/P	0.9913	likely_pathogenic	0.9938	pathogenic	-0.831	Destabilizing	0.92	D	0.663	neutral	None	None	None	None	N
V/Q	0.4169	ambiguous	0.4759	ambiguous	-1.313	Destabilizing	0.92	D	0.667	neutral	None	None	None	None	N
V/R	0.3895	ambiguous	0.4261	ambiguous	-1.073	Destabilizing	0.92	D	0.697	prob.neutral	None	None	None	None	N
V/S	0.4374	ambiguous	0.4627	ambiguous	-2.026	Highly Destabilizing	0.447	N	0.649	neutral	None	None	None	None	N
V/T	0.24	likely_benign	0.2306	benign	-1.73	Destabilizing	0.617	D	0.601	neutral	None	None	None	None	N
V/W	0.8667	likely_pathogenic	0.9089	pathogenic	-1.452	Destabilizing	0.992	D	0.69	prob.neutral	None	None	None	None	N
V/Y	0.7047	likely_pathogenic	0.7358	pathogenic	-1.057	Destabilizing	0.92	D	0.66	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.