TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29591	88996;88997;88998	chr2:178554576;178554575;178554574	chr2:179419303;179419302;179419301
N2AB	27950	84073;84074;84075	chr2:178554576;178554575;178554574	chr2:179419303;179419302;179419301
N2A	27023	81292;81293;81294	chr2:178554576;178554575;178554574	chr2:179419303;179419302;179419301
N2B	20526	61801;61802;61803	chr2:178554576;178554575;178554574	chr2:179419303;179419302;179419301
Novex-1	20651	62176;62177;62178	chr2:178554576;178554575;178554574	chr2:179419303;179419302;179419301
Novex-2	20718	62377;62378;62379	chr2:178554576;178554575;178554574	chr2:179419303;179419302;179419301
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-103
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.1181
• 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
C/Y	None	None	0.004	N	0.5	0.353	0.62347134366	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
C/A	0.432	ambiguous	0.469	ambiguous	-1.23	Destabilizing	0.25	N	0.444	neutral	None	None	None	None	N
C/D	0.6813	likely_pathogenic	0.726	pathogenic	-1.155	Destabilizing	0.85	D	0.621	neutral	None	None	None	None	N
C/E	0.746	likely_pathogenic	0.7922	pathogenic	-0.95	Destabilizing	0.85	D	0.619	neutral	None	None	None	None	N
C/F	0.4911	ambiguous	0.5328	ambiguous	-0.814	Destabilizing	0.681	D	0.589	neutral	N	0.465778788	None	None	N
C/G	0.1689	likely_benign	0.1999	benign	-1.548	Destabilizing	0.379	N	0.576	neutral	N	0.469248282	None	None	N
C/H	0.5636	ambiguous	0.637	pathogenic	-1.533	Destabilizing	0.85	D	0.676	prob.neutral	None	None	None	None	N
C/I	0.7519	likely_pathogenic	0.7684	pathogenic	-0.378	Destabilizing	0.85	D	0.508	neutral	None	None	None	None	N
C/K	0.7009	likely_pathogenic	0.7603	pathogenic	-0.67	Destabilizing	0.85	D	0.614	neutral	None	None	None	None	N
C/L	0.5056	ambiguous	0.5111	ambiguous	-0.378	Destabilizing	0.447	N	0.471	neutral	None	None	None	None	N
C/M	0.6396	likely_pathogenic	0.6549	pathogenic	0.522	Stabilizing	0.992	D	0.552	neutral	None	None	None	None	N
C/N	0.3058	likely_benign	0.3321	benign	-1.358	Destabilizing	0.85	D	0.637	neutral	None	None	None	None	N
C/P	0.6345	likely_pathogenic	0.6578	pathogenic	-0.641	Destabilizing	0.92	D	0.655	neutral	None	None	None	None	N
C/Q	0.5673	likely_pathogenic	0.6536	pathogenic	-0.979	Destabilizing	0.92	D	0.67	neutral	None	None	None	None	N
C/R	0.4109	ambiguous	0.502	ambiguous	-0.892	Destabilizing	0.81	D	0.653	neutral	N	0.492212133	None	None	N
C/S	0.3064	likely_benign	0.3668	ambiguous	-1.642	Destabilizing	0.016	N	0.396	neutral	N	0.503775921	None	None	N
C/T	0.3497	ambiguous	0.3559	ambiguous	-1.261	Destabilizing	0.447	N	0.452	neutral	None	None	None	None	N
C/V	0.6224	likely_pathogenic	0.635	pathogenic	-0.641	Destabilizing	0.617	D	0.453	neutral	None	None	None	None	N
C/W	0.752	likely_pathogenic	0.8094	pathogenic	-1.118	Destabilizing	0.97	D	0.64	neutral	N	0.496253307	None	None	N
C/Y	0.4472	ambiguous	0.4906	ambiguous	-0.902	Destabilizing	0.004	N	0.5	neutral	N	0.468487813	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.