TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21283	64072;64073;64074	chr2:178587364;178587363;178587362	chr2:179452091;179452090;179452089
N2AB	19642	59149;59150;59151	chr2:178587364;178587363;178587362	chr2:179452091;179452090;179452089
N2A	18715	56368;56369;56370	chr2:178587364;178587363;178587362	chr2:179452091;179452090;179452089
N2B	12218	36877;36878;36879	chr2:178587364;178587363;178587362	chr2:179452091;179452090;179452089
Novex-1	12343	37252;37253;37254	chr2:178587364;178587363;178587362	chr2:179452091;179452090;179452089
Novex-2	12410	37453;37454;37455	chr2:178587364;178587363;178587362	chr2:179452091;179452090;179452089
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: Fn3-42
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0917
• 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/R	rs1375757273	-1.649	0.994	N	0.819	0.451	0.800807230783	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
C/R	rs1375757273	-1.649	0.994	N	0.819	0.451	0.800807230783	gnomAD-4.0.0	1.59512E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4353E-05	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	0.3576	ambiguous	0.4181	ambiguous	-1.559	Destabilizing	0.055	N	0.233	neutral	None	None	None	None	N
C/D	0.9979	likely_pathogenic	0.9984	pathogenic	-1.801	Destabilizing	0.995	D	0.801	deleterious	None	None	None	None	N
C/E	0.9985	likely_pathogenic	0.9989	pathogenic	-1.576	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
C/F	0.7692	likely_pathogenic	0.8116	pathogenic	-1.17	Destabilizing	0.998	D	0.805	deleterious	N	0.513358197	None	None	N
C/G	0.4241	ambiguous	0.501	ambiguous	-1.902	Destabilizing	0.959	D	0.713	prob.delet.	N	0.477744205	None	None	N
C/H	0.9928	likely_pathogenic	0.9944	pathogenic	-2.364	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
C/I	0.6149	likely_pathogenic	0.6607	pathogenic	-0.646	Destabilizing	0.984	D	0.791	deleterious	None	None	None	None	N
C/K	0.999	likely_pathogenic	0.9993	pathogenic	-1.184	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
C/L	0.6042	likely_pathogenic	0.654	pathogenic	-0.646	Destabilizing	0.927	D	0.686	prob.neutral	None	None	None	None	N
C/M	0.8305	likely_pathogenic	0.8568	pathogenic	0.051	Stabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
C/N	0.9873	likely_pathogenic	0.9897	pathogenic	-1.804	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
C/P	0.9975	likely_pathogenic	0.9984	pathogenic	-0.927	Destabilizing	0.995	D	0.813	deleterious	None	None	None	None	N
C/Q	0.9934	likely_pathogenic	0.9948	pathogenic	-1.362	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
C/R	0.9901	likely_pathogenic	0.9922	pathogenic	-1.621	Destabilizing	0.994	D	0.819	deleterious	N	0.49584846	None	None	N
C/S	0.5905	likely_pathogenic	0.6497	pathogenic	-2.032	Highly Destabilizing	0.828	D	0.69	prob.neutral	N	0.46136147	None	None	N
C/T	0.7133	likely_pathogenic	0.7669	pathogenic	-1.625	Destabilizing	0.969	D	0.733	prob.delet.	None	None	None	None	N
C/V	0.4117	ambiguous	0.4572	ambiguous	-0.927	Destabilizing	0.927	D	0.703	prob.neutral	None	None	None	None	N
C/W	0.9856	likely_pathogenic	0.9895	pathogenic	-1.648	Destabilizing	0.999	D	0.757	deleterious	N	0.49584846	None	None	N
C/Y	0.9511	likely_pathogenic	0.9624	pathogenic	-1.375	Destabilizing	0.998	D	0.791	deleterious	N	0.484238665	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.