TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7653	23182;23183;23184	chr2:178721062;178721061;178721060	chr2:179585789;179585788;179585787
N2AB	7336	22231;22232;22233	chr2:178721062;178721061;178721060	chr2:179585789;179585788;179585787
N2A	6409	19450;19451;19452	chr2:178721062;178721061;178721060	chr2:179585789;179585788;179585787
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-61
• Domain position: 46
• Structural Position: 111
• Q(SASA): 1.1219
• 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
W/C	None	None	0.958	N	0.269	0.275	0.266843984389	gnomAD-4.0.0	6.84489E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16004E-05	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
W/A	0.1477	likely_benign	0.2103	benign	-1.134	Destabilizing	0.2	N	0.319	neutral	None	None	None	None	N
W/C	0.468	ambiguous	0.537	ambiguous	-0.17	Destabilizing	0.958	D	0.269	neutral	N	0.461171576	None	None	N
W/D	0.1918	likely_benign	0.3148	benign	0.649	Stabilizing	0.001	N	0.271	neutral	None	None	None	None	N
W/E	0.1903	likely_benign	0.3105	benign	0.688	Stabilizing	0.001	N	0.276	neutral	None	None	None	None	N
W/F	0.1938	likely_benign	0.235	benign	-0.548	Destabilizing	0.896	D	0.439	neutral	None	None	None	None	N
W/G	0.0873	likely_benign	0.1255	benign	-1.304	Destabilizing	None	N	0.261	neutral	N	0.329393596	None	None	N
W/H	0.234	likely_benign	0.334	benign	-0.052	Destabilizing	0.908	D	0.363	neutral	None	None	None	None	N
W/I	0.2473	likely_benign	0.3392	benign	-0.622	Destabilizing	0.738	D	0.449	neutral	None	None	None	None	N
W/K	0.204	likely_benign	0.3359	benign	-0.154	Destabilizing	0.111	N	0.347	neutral	None	None	None	None	N
W/L	0.1525	likely_benign	0.209	benign	-0.622	Destabilizing	0.302	N	0.323	neutral	N	0.404798219	None	None	N
W/M	0.2759	likely_benign	0.381	ambiguous	-0.459	Destabilizing	0.968	D	0.321	neutral	None	None	None	None	N
W/N	0.2204	likely_benign	0.3403	ambiguous	-0.479	Destabilizing	0.002	N	0.268	neutral	None	None	None	None	N
W/P	0.2232	likely_benign	0.3516	ambiguous	-0.79	Destabilizing	0.738	D	0.42	neutral	None	None	None	None	N
W/Q	0.2049	likely_benign	0.3034	benign	-0.339	Destabilizing	0.223	N	0.353	neutral	None	None	None	None	N
W/R	0.185	likely_benign	0.2784	benign	0.021	Stabilizing	0.001	N	0.273	neutral	N	0.323219772	None	None	N
W/S	0.0933	likely_benign	0.1426	benign	-0.917	Destabilizing	0.086	N	0.331	neutral	N	0.310250475	None	None	N
W/T	0.1449	likely_benign	0.2186	benign	-0.826	Destabilizing	0.365	N	0.305	neutral	None	None	None	None	N
W/V	0.1933	likely_benign	0.2634	benign	-0.79	Destabilizing	0.538	D	0.349	neutral	None	None	None	None	N
W/Y	0.2815	likely_benign	0.3445	ambiguous	-0.684	Destabilizing	0.896	D	0.46	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.