TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22308	67147;67148;67149	chr2:178580457;178580456;178580455	chr2:179445184;179445183;179445182
N2AB	20667	62224;62225;62226	chr2:178580457;178580456;178580455	chr2:179445184;179445183;179445182
N2A	19740	59443;59444;59445	chr2:178580457;178580456;178580455	chr2:179445184;179445183;179445182
N2B	13243	39952;39953;39954	chr2:178580457;178580456;178580455	chr2:179445184;179445183;179445182
Novex-1	13368	40327;40328;40329	chr2:178580457;178580456;178580455	chr2:179445184;179445183;179445182
Novex-2	13435	40528;40529;40530	chr2:178580457;178580456;178580455	chr2:179445184;179445183;179445182
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-126
• Domain position: 44
• Structural Position: 121
• Q(SASA): 0.352
• 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
L/P	None	None	1.0	N	0.825	0.725	0.718142918398	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
L/A	0.6115	likely_pathogenic	0.6329	pathogenic	-2.23	Highly Destabilizing	0.997	D	0.537	neutral	None	None	None	None	N
L/C	0.7108	likely_pathogenic	0.702	pathogenic	-1.643	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
L/D	0.9651	likely_pathogenic	0.9638	pathogenic	-1.9	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/E	0.876	likely_pathogenic	0.8693	pathogenic	-1.824	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/F	0.3026	likely_benign	0.2957	benign	-1.549	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
L/G	0.8794	likely_pathogenic	0.8822	pathogenic	-2.647	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/H	0.7739	likely_pathogenic	0.7644	pathogenic	-1.921	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/I	0.1161	likely_benign	0.115	benign	-1.104	Destabilizing	0.994	D	0.497	neutral	None	None	None	None	N
L/K	0.8235	likely_pathogenic	0.8112	pathogenic	-1.672	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/M	0.1653	likely_benign	0.1657	benign	-0.952	Destabilizing	0.999	D	0.753	deleterious	N	0.501891275	None	None	N
L/N	0.8245	likely_pathogenic	0.8218	pathogenic	-1.623	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/P	0.8894	likely_pathogenic	0.8877	pathogenic	-1.451	Destabilizing	1.0	D	0.825	deleterious	N	0.490153463	None	None	N
L/Q	0.6808	likely_pathogenic	0.6732	pathogenic	-1.721	Destabilizing	1.0	D	0.814	deleterious	N	0.50241135	None	None	N
L/R	0.7826	likely_pathogenic	0.7646	pathogenic	-1.13	Destabilizing	1.0	D	0.817	deleterious	N	0.502237992	None	None	N
L/S	0.7867	likely_pathogenic	0.7994	pathogenic	-2.323	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/T	0.5085	ambiguous	0.5248	ambiguous	-2.115	Highly Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
L/V	0.1429	likely_benign	0.1392	benign	-1.451	Destabilizing	0.767	D	0.374	neutral	N	0.440840029	None	None	N
L/W	0.6391	likely_pathogenic	0.6098	pathogenic	-1.698	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
L/Y	0.6902	likely_pathogenic	0.669	pathogenic	-1.471	Destabilizing	1.0	D	0.8	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.