TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24318	73177;73178;73179	chr2:178573180;178573179;178573178	chr2:179437907;179437906;179437905
N2AB	22677	68254;68255;68256	chr2:178573180;178573179;178573178	chr2:179437907;179437906;179437905
N2A	21750	65473;65474;65475	chr2:178573180;178573179;178573178	chr2:179437907;179437906;179437905
N2B	15253	45982;45983;45984	chr2:178573180;178573179;178573178	chr2:179437907;179437906;179437905
Novex-1	15378	46357;46358;46359	chr2:178573180;178573179;178573178	chr2:179437907;179437906;179437905
Novex-2	15445	46558;46559;46560	chr2:178573180;178573179;178573178	chr2:179437907;179437906;179437905
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-64
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.2825
• 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
C/R	rs1443412363	0.121	0.744	N	0.642	0.231	0.713796121269	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
C/R	rs1443412363	0.121	0.744	N	0.642	0.231	0.713796121269	gnomAD-4.0.0	2.74149E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60225E-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
C/A	0.1956	likely_benign	0.1577	benign	-1.058	Destabilizing	0.09	N	0.161	neutral	None	None	None	None	N
C/D	0.4841	ambiguous	0.3594	ambiguous	-0.386	Destabilizing	0.355	N	0.435	neutral	None	None	None	None	N
C/E	0.4729	ambiguous	0.3732	ambiguous	-0.359	Destabilizing	0.015	N	0.213	neutral	None	None	None	None	N
C/F	0.139	likely_benign	0.101	benign	-0.938	Destabilizing	0.744	D	0.601	neutral	N	0.488509805	None	None	N
C/G	0.1299	likely_benign	0.1029	benign	-1.273	Destabilizing	0.255	N	0.439	neutral	N	0.48710825	None	None	N
C/H	0.2658	likely_benign	0.2112	benign	-1.579	Destabilizing	0.96	D	0.493	neutral	None	None	None	None	N
C/I	0.2615	likely_benign	0.2152	benign	-0.553	Destabilizing	0.003	N	0.159	neutral	None	None	None	None	N
C/K	0.3677	ambiguous	0.3147	benign	-0.418	Destabilizing	0.524	D	0.463	neutral	None	None	None	None	N
C/L	0.2888	likely_benign	0.2276	benign	-0.553	Destabilizing	0.09	N	0.326	neutral	None	None	None	None	N
C/M	0.3453	ambiguous	0.2943	benign	-0.064	Destabilizing	0.794	D	0.363	neutral	None	None	None	None	N
C/N	0.2795	likely_benign	0.1992	benign	-0.274	Destabilizing	0.524	D	0.546	neutral	None	None	None	None	N
C/P	0.9616	likely_pathogenic	0.9338	pathogenic	-0.695	Destabilizing	0.887	D	0.604	neutral	None	None	None	None	N
C/Q	0.2632	likely_benign	0.2223	benign	-0.403	Destabilizing	0.794	D	0.631	neutral	None	None	None	None	N
C/R	0.1574	likely_benign	0.1349	benign	-0.248	Destabilizing	0.744	D	0.642	neutral	N	0.447896501	None	None	N
C/S	0.1329	likely_benign	0.1011	benign	-0.671	Destabilizing	0.013	N	0.136	neutral	N	0.521527468	None	None	N
C/T	0.2027	likely_benign	0.1685	benign	-0.501	Destabilizing	0.185	N	0.34	neutral	None	None	None	None	N
C/V	0.2145	likely_benign	0.1895	benign	-0.695	Destabilizing	0.006	N	0.123	neutral	None	None	None	None	N
C/W	0.3757	ambiguous	0.284	benign	-0.965	Destabilizing	0.985	D	0.491	neutral	N	0.500373089	None	None	N
C/Y	0.2072	likely_benign	0.1431	benign	-0.816	Destabilizing	0.947	D	0.577	neutral	N	0.488509805	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.