TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6467	19624;19625;19626	chr2:178728527;178728526;178728525	chr2:179593254;179593253;179593252
N2AB	6150	18673;18674;18675	chr2:178728527;178728526;178728525	chr2:179593254;179593253;179593252
N2A	5223	15892;15893;15894	chr2:178728527;178728526;178728525	chr2:179593254;179593253;179593252
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-48
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.3373
• 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/I	None	None	0.023	D	0.479	0.398	0.64410640661	gnomAD-4.0.0	6.85099E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00343E-07	0	0
S/R	rs1454652385	-0.286	0.642	N	0.563	0.371	0.360163838653	gnomAD-4.0.0	1.59575E-06	None	None	None	None	N	None	0	2.29537E-05	None	0	0	None	0	0	0	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	0.091	likely_benign	0.089	benign	-0.646	Destabilizing	0.176	N	0.339	neutral	None	None	None	None	N
S/C	0.1513	likely_benign	0.1506	benign	-0.425	Destabilizing	0.013	N	0.337	neutral	D	0.551872514	None	None	N
S/D	0.5295	ambiguous	0.4555	ambiguous	0.058	Stabilizing	0.543	D	0.471	neutral	None	None	None	None	N
S/E	0.5041	ambiguous	0.4629	ambiguous	0.023	Stabilizing	0.543	D	0.481	neutral	None	None	None	None	N
S/F	0.1662	likely_benign	0.1391	benign	-0.955	Destabilizing	0.944	D	0.601	neutral	None	None	None	None	N
S/G	0.1966	likely_benign	0.161	benign	-0.856	Destabilizing	0.425	N	0.475	neutral	D	0.551112045	None	None	N
S/H	0.3412	ambiguous	0.3113	benign	-1.328	Destabilizing	0.944	D	0.554	neutral	None	None	None	None	N
S/I	0.1708	likely_benign	0.1421	benign	-0.207	Destabilizing	0.023	N	0.479	neutral	D	0.52848834	None	None	N
S/K	0.6803	likely_pathogenic	0.6219	pathogenic	-0.649	Destabilizing	0.543	D	0.471	neutral	None	None	None	None	N
S/L	0.1202	likely_benign	0.1019	benign	-0.207	Destabilizing	0.329	N	0.499	neutral	None	None	None	None	N
S/M	0.2183	likely_benign	0.2081	benign	0.011	Stabilizing	0.944	D	0.553	neutral	None	None	None	None	N
S/N	0.2268	likely_benign	0.1802	benign	-0.489	Destabilizing	0.023	N	0.24	neutral	N	0.489215183	None	None	N
S/P	0.8874	likely_pathogenic	0.8101	pathogenic	-0.32	Destabilizing	0.944	D	0.58	neutral	None	None	None	None	N
S/Q	0.4816	ambiguous	0.4499	ambiguous	-0.65	Destabilizing	0.085	N	0.323	neutral	None	None	None	None	N
S/R	0.5764	likely_pathogenic	0.4935	ambiguous	-0.516	Destabilizing	0.642	D	0.563	neutral	N	0.506901365	None	None	N
S/T	0.0774	likely_benign	0.0762	benign	-0.549	Destabilizing	0.023	N	0.215	neutral	N	0.508755745	None	None	N
S/V	0.1573	likely_benign	0.1483	benign	-0.32	Destabilizing	0.329	N	0.51	neutral	None	None	None	None	N
S/W	0.3857	ambiguous	0.3277	benign	-0.928	Destabilizing	0.995	D	0.647	neutral	None	None	None	None	N
S/Y	0.1945	likely_benign	0.1615	benign	-0.669	Destabilizing	0.981	D	0.597	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.