TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33711	101356;101357;101358	chr2:178535484;178535483;178535482	chr2:179400211;179400210;179400209
N2AB	32070	96433;96434;96435	chr2:178535484;178535483;178535482	chr2:179400211;179400210;179400209
N2A	31143	93652;93653;93654	chr2:178535484;178535483;178535482	chr2:179400211;179400210;179400209
N2B	24646	74161;74162;74163	chr2:178535484;178535483;178535482	chr2:179400211;179400210;179400209
Novex-1	24771	74536;74537;74538	chr2:178535484;178535483;178535482	chr2:179400211;179400210;179400209
Novex-2	24838	74737;74738;74739	chr2:178535484;178535483;178535482	chr2:179400211;179400210;179400209
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-132
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.397
• 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
T/I	rs1248094195	0.06	0.001	N	0.188	0.142	0.202086224978	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
T/S	None	None	0.003	N	0.213	0.073	0.134241683229	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
T/A	0.0841	likely_benign	0.0846	benign	-0.893	Destabilizing	None	N	0.083	neutral	N	0.471325147	None	None	N
T/C	0.3337	likely_benign	0.3407	ambiguous	-0.611	Destabilizing	0.906	D	0.459	neutral	None	None	None	None	N
T/D	0.2909	likely_benign	0.3213	benign	-0.485	Destabilizing	0.026	N	0.311	neutral	None	None	None	None	N
T/E	0.2137	likely_benign	0.2228	benign	-0.459	Destabilizing	0.001	N	0.168	neutral	None	None	None	None	N
T/F	0.2574	likely_benign	0.2567	benign	-0.853	Destabilizing	0.848	D	0.615	neutral	None	None	None	None	N
T/G	0.2459	likely_benign	0.2478	benign	-1.183	Destabilizing	0.181	N	0.293	neutral	None	None	None	None	N
T/H	0.2343	likely_benign	0.2457	benign	-1.456	Destabilizing	0.676	D	0.515	neutral	None	None	None	None	N
T/I	0.1359	likely_benign	0.1361	benign	-0.202	Destabilizing	0.001	N	0.188	neutral	N	0.482619576	None	None	N
T/K	0.1784	likely_benign	0.1755	benign	-0.864	Destabilizing	0.11	N	0.317	neutral	None	None	None	None	N
T/L	0.0925	likely_benign	0.0929	benign	-0.202	Destabilizing	0.051	N	0.258	neutral	None	None	None	None	N
T/M	0.083	likely_benign	0.0831	benign	0.047	Stabilizing	0.676	D	0.465	neutral	None	None	None	None	N
T/N	0.0993	likely_benign	0.1109	benign	-0.89	Destabilizing	None	N	0.083	neutral	N	0.474037378	None	None	N
T/P	0.3706	ambiguous	0.3609	ambiguous	-0.4	Destabilizing	0.164	N	0.409	neutral	N	0.483298202	None	None	N
T/Q	0.1804	likely_benign	0.1826	benign	-1.013	Destabilizing	0.011	N	0.233	neutral	None	None	None	None	N
T/R	0.1635	likely_benign	0.149	benign	-0.657	Destabilizing	0.614	D	0.356	neutral	None	None	None	None	N
T/S	0.104	likely_benign	0.1109	benign	-1.152	Destabilizing	0.003	N	0.213	neutral	N	0.432091968	None	None	N
T/V	0.11	likely_benign	0.1117	benign	-0.4	Destabilizing	0.002	N	0.104	neutral	None	None	None	None	N
T/W	0.582	likely_pathogenic	0.5601	ambiguous	-0.804	Destabilizing	0.992	D	0.521	neutral	None	None	None	None	N
T/Y	0.3106	likely_benign	0.3011	benign	-0.572	Destabilizing	0.972	D	0.615	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.