TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30393	91402;91403;91404	chr2:178551723;178551722;178551721	chr2:179416450;179416449;179416448
N2AB	28752	86479;86480;86481	chr2:178551723;178551722;178551721	chr2:179416450;179416449;179416448
N2A	27825	83698;83699;83700	chr2:178551723;178551722;178551721	chr2:179416450;179416449;179416448
N2B	21328	64207;64208;64209	chr2:178551723;178551722;178551721	chr2:179416450;179416449;179416448
Novex-1	21453	64582;64583;64584	chr2:178551723;178551722;178551721	chr2:179416450;179416449;179416448
Novex-2	21520	64783;64784;64785	chr2:178551723;178551722;178551721	chr2:179416450;179416449;179416448
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: Fn3-109
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.3251
• 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	1.0	N	0.681	0.63	0.838516671336	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
L/A	0.6505	likely_pathogenic	0.5884	pathogenic	-1.815	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	I
L/C	0.7554	likely_pathogenic	0.7164	pathogenic	-0.914	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
L/D	0.9708	likely_pathogenic	0.9624	pathogenic	-1.323	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
L/E	0.8446	likely_pathogenic	0.8149	pathogenic	-1.274	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
L/F	0.429	ambiguous	0.406	ambiguous	-1.201	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
L/G	0.8859	likely_pathogenic	0.8476	pathogenic	-2.183	Highly Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
L/H	0.6707	likely_pathogenic	0.6162	pathogenic	-1.369	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
L/I	0.1752	likely_benign	0.1662	benign	-0.851	Destabilizing	0.999	D	0.445	neutral	None	None	None	None	I
L/K	0.7502	likely_pathogenic	0.6701	pathogenic	-1.223	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
L/M	0.1618	likely_benign	0.157	benign	-0.571	Destabilizing	1.0	D	0.671	neutral	N	0.499431681	None	None	I
L/N	0.7756	likely_pathogenic	0.7046	pathogenic	-1.124	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
L/P	0.9867	likely_pathogenic	0.988	pathogenic	-1.143	Destabilizing	1.0	D	0.681	prob.neutral	N	0.487484803	None	None	I
L/Q	0.4807	ambiguous	0.4235	ambiguous	-1.25	Destabilizing	1.0	D	0.695	prob.neutral	N	0.486059739	None	None	I
L/R	0.6273	likely_pathogenic	0.5597	ambiguous	-0.64	Destabilizing	1.0	D	0.693	prob.neutral	N	0.472821083	None	None	I
L/S	0.753	likely_pathogenic	0.6972	pathogenic	-1.759	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
L/T	0.5759	likely_pathogenic	0.5312	ambiguous	-1.594	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
L/V	0.2182	likely_benign	0.2046	benign	-1.143	Destabilizing	0.999	D	0.411	neutral	N	0.464068314	None	None	I
L/W	0.678	likely_pathogenic	0.6369	pathogenic	-1.352	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
L/Y	0.7493	likely_pathogenic	0.6949	pathogenic	-1.104	Destabilizing	1.0	D	0.68	prob.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.