TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22896	68911;68912;68913	chr2:178577740;178577739;178577738	chr2:179442467;179442466;179442465
N2AB	21255	63988;63989;63990	chr2:178577740;178577739;178577738	chr2:179442467;179442466;179442465
N2A	20328	61207;61208;61209	chr2:178577740;178577739;178577738	chr2:179442467;179442466;179442465
N2B	13831	41716;41717;41718	chr2:178577740;178577739;178577738	chr2:179442467;179442466;179442465
Novex-1	13956	42091;42092;42093	chr2:178577740;178577739;178577738	chr2:179442467;179442466;179442465
Novex-2	14023	42292;42293;42294	chr2:178577740;178577739;178577738	chr2:179442467;179442466;179442465
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-54
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1005
• 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
V/F	None	None	0.97	N	0.685	0.504	0.706391083165	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
V/A	0.7213	likely_pathogenic	0.7543	pathogenic	-1.745	Destabilizing	0.822	D	0.579	neutral	N	0.478805205	None	None	N
V/C	0.866	likely_pathogenic	0.8692	pathogenic	-1.159	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
V/D	0.9605	likely_pathogenic	0.9687	pathogenic	-2.133	Highly Destabilizing	0.89	D	0.733	prob.delet.	N	0.513990211	None	None	N
V/E	0.9126	likely_pathogenic	0.9241	pathogenic	-1.943	Destabilizing	0.956	D	0.665	neutral	None	None	None	None	N
V/F	0.6713	likely_pathogenic	0.7102	pathogenic	-1.076	Destabilizing	0.97	D	0.685	prob.neutral	N	0.507775694	None	None	N
V/G	0.8597	likely_pathogenic	0.8782	pathogenic	-2.256	Highly Destabilizing	0.89	D	0.723	prob.delet.	N	0.473035215	None	None	N
V/H	0.9629	likely_pathogenic	0.9683	pathogenic	-2.103	Highly Destabilizing	0.994	D	0.751	deleterious	None	None	None	None	N
V/I	0.0809	likely_benign	0.0835	benign	-0.344	Destabilizing	0.058	N	0.255	neutral	N	0.45054723	None	None	N
V/K	0.9317	likely_pathogenic	0.9379	pathogenic	-1.404	Destabilizing	0.956	D	0.669	neutral	None	None	None	None	N
V/L	0.4516	ambiguous	0.4923	ambiguous	-0.344	Destabilizing	0.489	N	0.527	neutral	D	0.524639557	None	None	N
V/M	0.4433	ambiguous	0.4817	ambiguous	-0.303	Destabilizing	0.978	D	0.651	neutral	None	None	None	None	N
V/N	0.8764	likely_pathogenic	0.8951	pathogenic	-1.617	Destabilizing	0.043	N	0.581	neutral	None	None	None	None	N
V/P	0.964	likely_pathogenic	0.9653	pathogenic	-0.781	Destabilizing	0.993	D	0.682	prob.neutral	None	None	None	None	N
V/Q	0.8996	likely_pathogenic	0.9089	pathogenic	-1.49	Destabilizing	0.956	D	0.698	prob.neutral	None	None	None	None	N
V/R	0.9092	likely_pathogenic	0.9144	pathogenic	-1.267	Destabilizing	0.956	D	0.754	deleterious	None	None	None	None	N
V/S	0.8101	likely_pathogenic	0.833	pathogenic	-2.222	Highly Destabilizing	0.915	D	0.683	prob.neutral	None	None	None	None	N
V/T	0.7347	likely_pathogenic	0.7619	pathogenic	-1.891	Destabilizing	0.86	D	0.624	neutral	None	None	None	None	N
V/W	0.9883	likely_pathogenic	0.9896	pathogenic	-1.607	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
V/Y	0.9418	likely_pathogenic	0.9476	pathogenic	-1.166	Destabilizing	0.993	D	0.67	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.