TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33381	100366;100367;100368	chr2:178536968;178536967;178536966	chr2:179401695;179401694;179401693
N2AB	31740	95443;95444;95445	chr2:178536968;178536967;178536966	chr2:179401695;179401694;179401693
N2A	30813	92662;92663;92664	chr2:178536968;178536967;178536966	chr2:179401695;179401694;179401693
N2B	24316	73171;73172;73173	chr2:178536968;178536967;178536966	chr2:179401695;179401694;179401693
Novex-1	24441	73546;73547;73548	chr2:178536968;178536967;178536966	chr2:179401695;179401694;179401693
Novex-2	24508	73747;73748;73749	chr2:178536968;178536967;178536966	chr2:179401695;179401694;179401693
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-130
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.8831
• Predicted PPI site: I

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	None	None	0.303	N	0.487	0.378	0.634884455959	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
S/P	None	None	None	N	0.107	0.122	0.0297737177859	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.08	likely_benign	0.0706	benign	-0.233	Destabilizing	None	N	0.079	neutral	N	0.512435477	None	None	I
S/C	0.2452	likely_benign	0.167	benign	-0.669	Destabilizing	0.621	D	0.417	neutral	N	0.495496519	None	None	I
S/D	0.2387	likely_benign	0.2486	benign	-0.219	Destabilizing	0.075	N	0.34	neutral	None	None	None	None	I
S/E	0.2882	likely_benign	0.3005	benign	-0.316	Destabilizing	0.075	N	0.371	neutral	None	None	None	None	I
S/F	0.3986	ambiguous	0.2945	benign	-0.996	Destabilizing	0.303	N	0.487	neutral	N	0.483126256	None	None	I
S/G	0.1287	likely_benign	0.1236	benign	-0.228	Destabilizing	0.016	N	0.388	neutral	None	None	None	None	I
S/H	0.3119	likely_benign	0.2717	benign	-0.4	Destabilizing	0.637	D	0.423	neutral	None	None	None	None	I
S/I	0.3031	likely_benign	0.2376	benign	-0.359	Destabilizing	0.125	N	0.525	neutral	None	None	None	None	I
S/K	0.444	ambiguous	0.4315	ambiguous	-0.522	Destabilizing	0.075	N	0.365	neutral	None	None	None	None	I
S/L	0.1737	likely_benign	0.1354	benign	-0.359	Destabilizing	0.039	N	0.439	neutral	None	None	None	None	I
S/M	0.3042	likely_benign	0.2517	benign	-0.442	Destabilizing	0.366	N	0.431	neutral	None	None	None	None	I
S/N	0.1338	likely_benign	0.133	benign	-0.395	Destabilizing	0.075	N	0.444	neutral	None	None	None	None	I
S/P	0.0591	likely_benign	0.0565	benign	-0.3	Destabilizing	None	N	0.107	neutral	N	0.46578247	None	None	I
S/Q	0.2787	likely_benign	0.2703	benign	-0.547	Destabilizing	0.366	N	0.435	neutral	None	None	None	None	I
S/R	0.4596	ambiguous	0.4249	ambiguous	-0.296	Destabilizing	0.221	N	0.552	neutral	None	None	None	None	I
S/T	0.1056	likely_benign	0.0915	benign	-0.511	Destabilizing	None	N	0.121	neutral	N	0.420680109	None	None	I
S/V	0.2818	likely_benign	0.2258	benign	-0.3	Destabilizing	0.039	N	0.467	neutral	None	None	None	None	I
S/W	0.5766	likely_pathogenic	0.4755	ambiguous	-1.117	Destabilizing	0.869	D	0.469	neutral	None	None	None	None	I
S/Y	0.3349	likely_benign	0.2641	benign	-0.81	Destabilizing	0.303	N	0.471	neutral	N	0.494736051	None	None	I

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.