TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27545	82858;82859;82860	chr2:178563499;178563498;178563497	chr2:179428226;179428225;179428224
N2AB	25904	77935;77936;77937	chr2:178563499;178563498;178563497	chr2:179428226;179428225;179428224
N2A	24977	75154;75155;75156	chr2:178563499;178563498;178563497	chr2:179428226;179428225;179428224
N2B	18480	55663;55664;55665	chr2:178563499;178563498;178563497	chr2:179428226;179428225;179428224
Novex-1	18605	56038;56039;56040	chr2:178563499;178563498;178563497	chr2:179428226;179428225;179428224
Novex-2	18672	56239;56240;56241	chr2:178563499;178563498;178563497	chr2:179428226;179428225;179428224
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-88
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.114
• 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
A/T	rs770320388	-1.689	0.09	N	0.68	0.055	0.19670166235	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
A/T	rs770320388	-1.689	0.09	N	0.68	0.055	0.19670166235	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85827E-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
A/C	0.2461	likely_benign	0.2512	benign	-1.47	Destabilizing	0.944	D	0.744	deleterious	None	None	None	None	N
A/D	0.6635	likely_pathogenic	0.6607	pathogenic	-2.875	Highly Destabilizing	0.324	N	0.724	prob.delet.	N	0.492893308	None	None	N
A/E	0.4966	ambiguous	0.4742	ambiguous	-2.629	Highly Destabilizing	0.241	N	0.743	deleterious	None	None	None	None	N
A/F	0.2249	likely_benign	0.2168	benign	-0.723	Destabilizing	0.002	N	0.655	neutral	None	None	None	None	N
A/G	0.1742	likely_benign	0.1984	benign	-1.907	Destabilizing	0.09	N	0.714	prob.delet.	N	0.486816921	None	None	N
A/H	0.4885	ambiguous	0.4697	ambiguous	-2.288	Highly Destabilizing	0.818	D	0.738	prob.delet.	None	None	None	None	N
A/I	0.24	likely_benign	0.2565	benign	0.005	Stabilizing	0.241	N	0.771	deleterious	None	None	None	None	N
A/K	0.5944	likely_pathogenic	0.5901	pathogenic	-1.448	Destabilizing	0.241	N	0.741	deleterious	None	None	None	None	N
A/L	0.1399	likely_benign	0.1538	benign	0.005	Stabilizing	0.116	N	0.733	prob.delet.	None	None	None	None	N
A/M	0.1441	likely_benign	0.1557	benign	-0.409	Destabilizing	0.818	D	0.763	deleterious	None	None	None	None	N
A/N	0.418	ambiguous	0.4267	ambiguous	-1.902	Destabilizing	0.241	N	0.75	deleterious	None	None	None	None	N
A/P	0.9713	likely_pathogenic	0.9799	pathogenic	-0.422	Destabilizing	0.627	D	0.789	deleterious	N	0.505174666	None	None	N
A/Q	0.3862	ambiguous	0.3857	ambiguous	-1.621	Destabilizing	0.69	D	0.793	deleterious	None	None	None	None	N
A/R	0.4829	ambiguous	0.4722	ambiguous	-1.58	Destabilizing	0.69	D	0.785	deleterious	None	None	None	None	N
A/S	0.0796	likely_benign	0.079	benign	-2.282	Highly Destabilizing	None	N	0.281	neutral	N	0.405081512	None	None	N
A/T	0.0819	likely_benign	0.0861	benign	-1.91	Destabilizing	0.09	N	0.68	prob.neutral	N	0.478827122	None	None	N
A/V	0.1316	likely_benign	0.1384	benign	-0.422	Destabilizing	0.324	N	0.715	prob.delet.	N	0.484291657	None	None	N
A/W	0.571	likely_pathogenic	0.56	ambiguous	-1.564	Destabilizing	0.981	D	0.763	deleterious	None	None	None	None	N
A/Y	0.3527	ambiguous	0.3275	benign	-1.052	Destabilizing	0.527	D	0.757	deleterious	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.