TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20314	61165;61166;61167	chr2:178590785;178590784;178590783	chr2:179455512;179455511;179455510
N2AB	18673	56242;56243;56244	chr2:178590785;178590784;178590783	chr2:179455512;179455511;179455510
N2A	17746	53461;53462;53463	chr2:178590785;178590784;178590783	chr2:179455512;179455511;179455510
N2B	11249	33970;33971;33972	chr2:178590785;178590784;178590783	chr2:179455512;179455511;179455510
Novex-1	11374	34345;34346;34347	chr2:178590785;178590784;178590783	chr2:179455512;179455511;179455510
Novex-2	11441	34546;34547;34548	chr2:178590785;178590784;178590783	chr2:179455512;179455511;179455510
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: Fn3-35
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.8609
• 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/P	None	None	0.891	N	0.327	0.208	0.270447802918	gnomAD-4.0.0	1.37456E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80706E-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	0.0837	likely_benign	0.0852	benign	-0.166	Destabilizing	0.267	N	0.184	neutral	N	0.468591486	None	None	N
T/C	0.3252	likely_benign	0.3542	ambiguous	-0.453	Destabilizing	0.998	D	0.279	neutral	None	None	None	None	N
T/D	0.3232	likely_benign	0.3405	ambiguous	-0.048	Destabilizing	0.842	D	0.329	neutral	None	None	None	None	N
T/E	0.3157	likely_benign	0.3253	benign	-0.14	Destabilizing	0.842	D	0.323	neutral	None	None	None	None	N
T/F	0.2431	likely_benign	0.2744	benign	-0.829	Destabilizing	0.991	D	0.319	neutral	None	None	None	None	N
T/G	0.161	likely_benign	0.1644	benign	-0.217	Destabilizing	0.002	N	0.205	neutral	None	None	None	None	N
T/H	0.2126	likely_benign	0.2425	benign	-0.343	Destabilizing	0.991	D	0.293	neutral	None	None	None	None	N
T/I	0.2746	likely_benign	0.2806	benign	-0.153	Destabilizing	0.966	D	0.316	neutral	N	0.479295276	None	None	N
T/K	0.2204	likely_benign	0.2427	benign	-0.336	Destabilizing	0.842	D	0.341	neutral	None	None	None	None	N
T/L	0.1166	likely_benign	0.1303	benign	-0.153	Destabilizing	0.842	D	0.322	neutral	None	None	None	None	N
T/M	0.0926	likely_benign	0.1	benign	-0.214	Destabilizing	0.991	D	0.277	neutral	None	None	None	None	N
T/N	0.0986	likely_benign	0.105	benign	-0.174	Destabilizing	0.801	D	0.313	neutral	N	0.449405506	None	None	N
T/P	0.1761	likely_benign	0.1848	benign	-0.134	Destabilizing	0.891	D	0.327	neutral	N	0.479077839	None	None	N
T/Q	0.2263	likely_benign	0.2429	benign	-0.375	Destabilizing	0.974	D	0.314	neutral	None	None	None	None	N
T/R	0.1742	likely_benign	0.2092	benign	-0.034	Destabilizing	0.842	D	0.343	neutral	None	None	None	None	N
T/S	0.0823	likely_benign	0.0849	benign	-0.329	Destabilizing	0.007	N	0.113	neutral	N	0.380375069	None	None	N
T/V	0.2139	likely_benign	0.219	benign	-0.134	Destabilizing	0.842	D	0.295	neutral	None	None	None	None	N
T/W	0.4719	ambiguous	0.5353	ambiguous	-0.921	Destabilizing	0.998	D	0.324	neutral	None	None	None	None	N
T/Y	0.2692	likely_benign	0.2985	benign	-0.6	Destabilizing	0.991	D	0.301	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.