TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23741	71446;71447;71448	chr2:178574911;178574910;178574909	chr2:179439638;179439637;179439636
N2AB	22100	66523;66524;66525	chr2:178574911;178574910;178574909	chr2:179439638;179439637;179439636
N2A	21173	63742;63743;63744	chr2:178574911;178574910;178574909	chr2:179439638;179439637;179439636
N2B	14676	44251;44252;44253	chr2:178574911;178574910;178574909	chr2:179439638;179439637;179439636
Novex-1	14801	44626;44627;44628	chr2:178574911;178574910;178574909	chr2:179439638;179439637;179439636
Novex-2	14868	44827;44828;44829	chr2:178574911;178574910;178574909	chr2:179439638;179439637;179439636
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-60
• Domain position: 16
• Structural Position: 17
• Q(SASA): 0.2023
• 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
S/F	rs1709521259	None	0.979	D	0.536	0.307	0.462982567029	gnomAD-4.0.0	1.36922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79948E-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
S/A	0.0723	likely_benign	0.0686	benign	-0.99	Destabilizing	0.012	N	0.087	neutral	N	0.387381186	None	None	N
S/C	0.0694	likely_benign	0.0625	benign	-0.865	Destabilizing	0.003	N	0.159	neutral	N	0.480390134	None	None	N
S/D	0.6281	likely_pathogenic	0.6317	pathogenic	-1.053	Destabilizing	0.854	D	0.401	neutral	None	None	None	None	N
S/E	0.6493	likely_pathogenic	0.6724	pathogenic	-1.003	Destabilizing	0.742	D	0.368	neutral	None	None	None	None	N
S/F	0.4032	ambiguous	0.358	ambiguous	-1.207	Destabilizing	0.979	D	0.536	neutral	D	0.528605369	None	None	N
S/G	0.0933	likely_benign	0.0889	benign	-1.246	Destabilizing	0.543	D	0.372	neutral	None	None	None	None	N
S/H	0.4392	ambiguous	0.4571	ambiguous	-1.669	Destabilizing	0.996	D	0.467	neutral	None	None	None	None	N
S/I	0.2408	likely_benign	0.2074	benign	-0.395	Destabilizing	0.742	D	0.504	neutral	None	None	None	None	N
S/K	0.6811	likely_pathogenic	0.7029	pathogenic	-0.683	Destabilizing	0.742	D	0.348	neutral	None	None	None	None	N
S/L	0.1633	likely_benign	0.1417	benign	-0.395	Destabilizing	0.59	D	0.484	neutral	None	None	None	None	N
S/M	0.2472	likely_benign	0.222	benign	-0.131	Destabilizing	0.984	D	0.475	neutral	None	None	None	None	N
S/N	0.1735	likely_benign	0.1733	benign	-0.908	Destabilizing	0.854	D	0.436	neutral	None	None	None	None	N
S/P	0.2476	likely_benign	0.2648	benign	-0.562	Destabilizing	0.007	N	0.213	neutral	N	0.441234313	None	None	N
S/Q	0.5114	ambiguous	0.5328	ambiguous	-1.062	Destabilizing	0.953	D	0.435	neutral	None	None	None	None	N
S/R	0.5586	ambiguous	0.5831	pathogenic	-0.615	Destabilizing	0.953	D	0.461	neutral	None	None	None	None	N
S/T	0.1309	likely_benign	0.1175	benign	-0.826	Destabilizing	0.472	N	0.397	neutral	N	0.480734064	None	None	N
S/V	0.2316	likely_benign	0.1995	benign	-0.562	Destabilizing	0.742	D	0.482	neutral	None	None	None	None	N
S/W	0.5176	ambiguous	0.4966	ambiguous	-1.209	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	N
S/Y	0.3161	likely_benign	0.2975	benign	-0.895	Destabilizing	0.979	D	0.543	neutral	N	0.517484298	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.