TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8699	26320;26321;26322	chr2:178715091;178715090;178715089	chr2:179579818;179579817;179579816
N2AB	8382	25369;25370;25371	chr2:178715091;178715090;178715089	chr2:179579818;179579817;179579816
N2A	7455	22588;22589;22590	chr2:178715091;178715090;178715089	chr2:179579818;179579817;179579816
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-72
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1097
• 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
S/G	rs1164228016	-1.397	0.998	N	0.573	0.462	0.457286136841	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/G	rs1164228016	-1.397	0.998	N	0.573	0.462	0.457286136841	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	0
S/N	rs1311071697	None	0.973	D	0.59	0.22	None	gnomAD-4.0.0	1.23162E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.61914E-05	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
S/A	0.1121	likely_benign	0.1053	benign	-0.643	Destabilizing	0.939	D	0.507	neutral	None	None	None	None	N
S/C	0.2095	likely_benign	0.2037	benign	-0.516	Destabilizing	1.0	D	0.682	prob.neutral	N	0.507866097	None	None	N
S/D	0.7619	likely_pathogenic	0.6961	pathogenic	-1.812	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
S/E	0.8178	likely_pathogenic	0.7877	pathogenic	-1.577	Destabilizing	0.998	D	0.609	neutral	None	None	None	None	N
S/F	0.464	ambiguous	0.4199	ambiguous	-0.229	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
S/G	0.1623	likely_benign	0.1249	benign	-1.043	Destabilizing	0.998	D	0.573	neutral	N	0.495749323	None	None	N
S/H	0.5395	ambiguous	0.4994	ambiguous	-1.458	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
S/I	0.4503	ambiguous	0.3694	ambiguous	0.395	Stabilizing	1.0	D	0.693	prob.neutral	N	0.495015308	None	None	N
S/K	0.8828	likely_pathogenic	0.8452	pathogenic	-0.33	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	N
S/L	0.2611	likely_benign	0.2355	benign	0.395	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
S/M	0.3821	ambiguous	0.3503	ambiguous	0.171	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
S/N	0.3313	likely_benign	0.2728	benign	-1.21	Destabilizing	0.973	D	0.59	neutral	D	0.532944901	None	None	N
S/P	0.9838	likely_pathogenic	0.9732	pathogenic	0.081	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
S/Q	0.7263	likely_pathogenic	0.6927	pathogenic	-0.716	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
S/R	0.7779	likely_pathogenic	0.7178	pathogenic	-0.971	Destabilizing	1.0	D	0.687	prob.neutral	D	0.528576444	None	None	N
S/T	0.1301	likely_benign	0.119	benign	-0.756	Destabilizing	0.016	N	0.317	neutral	N	0.457596206	None	None	N
S/V	0.3641	ambiguous	0.3184	benign	0.081	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	N
S/W	0.615	likely_pathogenic	0.5708	pathogenic	-0.797	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
S/Y	0.3754	ambiguous	0.348	ambiguous	-0.305	Destabilizing	1.0	D	0.723	prob.delet.	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.