TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4680	14263;14264;14265	chr2:178739195;178739194;178739193	chr2:179603922;179603921;179603920
N2AB	4363	13312;13313;13314	chr2:178739195;178739194;178739193	chr2:179603922;179603921;179603920
N2A	None	None	chr2:None	chr2:None
N2B	4317	13174;13175;13176	chr2:178739195;178739194;178739193	chr2:179603922;179603921;179603920
Novex-1	4442	13549;13550;13551	chr2:178739195;178739194;178739193	chr2:179603922;179603921;179603920
Novex-2	4509	13750;13751;13752	chr2:178739195;178739194;178739193	chr2:179603922;179603921;179603920
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-29
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.4253
• 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/S	None	None	None	N	0.291	0.09	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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
L/A	0.1046	likely_benign	0.1199	benign	-2.047	Highly Destabilizing	0.007	N	0.331	neutral	None	None	None	None	N
L/C	0.242	likely_benign	0.2514	benign	-1.37	Destabilizing	0.676	D	0.447	neutral	None	None	None	None	N
L/D	0.3725	ambiguous	0.4168	ambiguous	-2.412	Highly Destabilizing	0.038	N	0.473	neutral	None	None	None	None	N
L/E	0.1461	likely_benign	0.1554	benign	-2.384	Highly Destabilizing	None	N	0.267	neutral	None	None	None	None	N
L/F	0.0831	likely_benign	0.0837	benign	-1.489	Destabilizing	0.171	N	0.385	neutral	N	0.481910722	None	None	N
L/G	0.2386	likely_benign	0.2834	benign	-2.395	Highly Destabilizing	0.038	N	0.468	neutral	None	None	None	None	N
L/H	0.0995	likely_benign	0.1022	benign	-1.644	Destabilizing	0.214	N	0.49	neutral	None	None	None	None	N
L/I	0.0716	likely_benign	0.0723	benign	-1.126	Destabilizing	None	N	0.101	neutral	None	None	None	None	N
L/K	0.1022	likely_benign	0.1025	benign	-1.425	Destabilizing	0.016	N	0.435	neutral	None	None	None	None	N
L/M	0.0796	likely_benign	0.0809	benign	-0.889	Destabilizing	0.171	N	0.414	neutral	N	0.504000445	None	None	N
L/N	0.1747	likely_benign	0.1928	benign	-1.376	Destabilizing	0.038	N	0.539	neutral	None	None	None	None	N
L/P	0.7644	likely_pathogenic	0.821	pathogenic	-1.407	Destabilizing	0.072	N	0.525	neutral	None	None	None	None	N
L/Q	0.0725	likely_benign	0.0738	benign	-1.588	Destabilizing	0.001	N	0.359	neutral	None	None	None	None	N
L/R	0.091	likely_benign	0.0935	benign	-0.807	Destabilizing	0.038	N	0.508	neutral	None	None	None	None	N
L/S	0.076	likely_benign	0.0893	benign	-1.908	Destabilizing	None	N	0.291	neutral	N	0.393865624	None	None	N
L/T	0.081	likely_benign	0.0911	benign	-1.775	Destabilizing	0.016	N	0.389	neutral	None	None	None	None	N
L/V	0.0663	likely_benign	0.0676	benign	-1.407	Destabilizing	None	N	0.105	neutral	N	0.412876673	None	None	N
L/W	0.0925	likely_benign	0.1029	benign	-1.657	Destabilizing	0.828	D	0.485	neutral	N	0.498572199	None	None	N
L/Y	0.1685	likely_benign	0.1803	benign	-1.432	Destabilizing	0.356	N	0.466	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.