TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4713	14362;14363;14364	chr2:178738316;178738315;178738314	chr2:179603043;179603042;179603041
N2AB	4396	13411;13412;13413	chr2:178738316;178738315;178738314	chr2:179603043;179603042;179603041
N2A	3469	10630;10631;10632	chr2:178738316;178738315;178738314	chr2:179603043;179603042;179603041
N2B	4350	13273;13274;13275	chr2:178738316;178738315;178738314	chr2:179603043;179603042;179603041
Novex-1	4475	13648;13649;13650	chr2:178738316;178738315;178738314	chr2:179603043;179603042;179603041
Novex-2	4542	13849;13850;13851	chr2:178738316;178738315;178738314	chr2:179603043;179603042;179603041
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-30
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.5679
• 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
L/P	None	None	0.989	N	0.387	0.316	0.561446168695	gnomAD-4.0.0	1.59221E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85938E-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
L/A	0.3867	ambiguous	0.3344	benign	-1.031	Destabilizing	0.525	D	0.336	neutral	None	None	None	None	I
L/C	0.8249	likely_pathogenic	0.7651	pathogenic	-0.588	Destabilizing	0.998	D	0.266	neutral	None	None	None	None	I
L/D	0.9389	likely_pathogenic	0.9168	pathogenic	-0.432	Destabilizing	0.728	D	0.389	neutral	None	None	None	None	I
L/E	0.6249	likely_pathogenic	0.5761	pathogenic	-0.507	Destabilizing	0.067	N	0.216	neutral	None	None	None	None	I
L/F	0.3591	ambiguous	0.3099	benign	-0.928	Destabilizing	0.949	D	0.298	neutral	None	None	None	None	I
L/G	0.8241	likely_pathogenic	0.7926	pathogenic	-1.255	Destabilizing	0.915	D	0.389	neutral	None	None	None	None	I
L/H	0.6022	likely_pathogenic	0.5326	ambiguous	-0.523	Destabilizing	0.998	D	0.311	neutral	None	None	None	None	I
L/I	0.1417	likely_benign	0.1137	benign	-0.541	Destabilizing	0.029	N	0.129	neutral	None	None	None	None	I
L/K	0.5172	ambiguous	0.5082	ambiguous	-0.552	Destabilizing	0.842	D	0.407	neutral	None	None	None	None	I
L/M	0.2063	likely_benign	0.1839	benign	-0.361	Destabilizing	0.966	D	0.311	neutral	N	0.44252616	None	None	I
L/N	0.7804	likely_pathogenic	0.7234	pathogenic	-0.251	Destabilizing	0.974	D	0.385	neutral	None	None	None	None	I
L/P	0.6957	likely_pathogenic	0.6291	pathogenic	-0.67	Destabilizing	0.989	D	0.387	neutral	N	0.453027599	None	None	I
L/Q	0.3567	ambiguous	0.3387	benign	-0.504	Destabilizing	0.934	D	0.362	neutral	N	0.454019937	None	None	I
L/R	0.4012	ambiguous	0.3881	ambiguous	0.057	Stabilizing	0.934	D	0.36	neutral	N	0.452365829	None	None	I
L/S	0.5679	likely_pathogenic	0.4769	ambiguous	-0.776	Destabilizing	0.842	D	0.37	neutral	None	None	None	None	I
L/T	0.4568	ambiguous	0.3513	ambiguous	-0.74	Destabilizing	0.842	D	0.307	neutral	None	None	None	None	I
L/V	0.1261	likely_benign	0.0999	benign	-0.67	Destabilizing	0.002	N	0.063	neutral	N	0.389917341	None	None	I
L/W	0.5669	likely_pathogenic	0.5152	ambiguous	-0.937	Destabilizing	0.998	D	0.366	neutral	None	None	None	None	I
L/Y	0.7183	likely_pathogenic	0.683	pathogenic	-0.697	Destabilizing	0.974	D	0.302	neutral	None	None	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.