TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30259	91000;91001;91002	chr2:178552125;178552124;178552123	chr2:179416852;179416851;179416850
N2AB	28618	86077;86078;86079	chr2:178552125;178552124;178552123	chr2:179416852;179416851;179416850
N2A	27691	83296;83297;83298	chr2:178552125;178552124;178552123	chr2:179416852;179416851;179416850
N2B	21194	63805;63806;63807	chr2:178552125;178552124;178552123	chr2:179416852;179416851;179416850
Novex-1	21319	64180;64181;64182	chr2:178552125;178552124;178552123	chr2:179416852;179416851;179416850
Novex-2	21386	64381;64382;64383	chr2:178552125;178552124;178552123	chr2:179416852;179416851;179416850
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-108
• Domain position: 36
• Structural Position: 37
• Q(SASA): 0.1602
• 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/W	rs1699680559	None	0.99	N	0.646	0.358	0.403896168776	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	1.90042E-04	0	None	0	0	None	0	0	0	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	0.4045	ambiguous	0.4767	ambiguous	-1.075	Destabilizing	0.25	N	0.457	neutral	None	None	None	None	N
C/D	0.9109	likely_pathogenic	0.9094	pathogenic	-0.257	Destabilizing	0.85	D	0.683	prob.neutral	None	None	None	None	N
C/E	0.9612	likely_pathogenic	0.9634	pathogenic	-0.187	Destabilizing	0.85	D	0.689	prob.neutral	None	None	None	None	N
C/F	0.6317	likely_pathogenic	0.5691	pathogenic	-0.956	Destabilizing	0.896	D	0.657	neutral	N	0.46674326	None	None	N
C/G	0.1095	likely_benign	0.1667	benign	-1.318	Destabilizing	0.002	N	0.429	neutral	N	0.342331182	None	None	N
C/H	0.7623	likely_pathogenic	0.7061	pathogenic	-1.736	Destabilizing	0.977	D	0.687	prob.neutral	None	None	None	None	N
C/I	0.9217	likely_pathogenic	0.9163	pathogenic	-0.49	Destabilizing	0.92	D	0.625	neutral	None	None	None	None	N
C/K	0.9662	likely_pathogenic	0.9606	pathogenic	-0.22	Destabilizing	0.739	D	0.689	prob.neutral	None	None	None	None	N
C/L	0.7835	likely_pathogenic	0.7909	pathogenic	-0.49	Destabilizing	0.617	D	0.558	neutral	None	None	None	None	N
C/M	0.8496	likely_pathogenic	0.8485	pathogenic	-0.177	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	N
C/N	0.5036	ambiguous	0.4869	ambiguous	-0.207	Destabilizing	0.739	D	0.689	prob.neutral	None	None	None	None	N
C/P	0.9978	likely_pathogenic	0.9972	pathogenic	-0.659	Destabilizing	0.92	D	0.71	prob.delet.	None	None	None	None	N
C/Q	0.8565	likely_pathogenic	0.8572	pathogenic	-0.224	Destabilizing	0.85	D	0.719	prob.delet.	None	None	None	None	N
C/R	0.8243	likely_pathogenic	0.8025	pathogenic	-0.298	Destabilizing	0.81	D	0.713	prob.delet.	N	0.424240489	None	None	N
C/S	0.2261	likely_benign	0.2699	benign	-0.597	Destabilizing	0.016	N	0.434	neutral	N	0.381700433	None	None	N
C/T	0.6437	likely_pathogenic	0.662	pathogenic	-0.363	Destabilizing	0.447	N	0.568	neutral	None	None	None	None	N
C/V	0.82	likely_pathogenic	0.8054	pathogenic	-0.659	Destabilizing	0.617	D	0.605	neutral	None	None	None	None	N
C/W	0.8889	likely_pathogenic	0.8773	pathogenic	-1.049	Destabilizing	0.99	D	0.646	neutral	N	0.510283393	None	None	N
C/Y	0.6563	likely_pathogenic	0.6305	pathogenic	-0.842	Destabilizing	0.963	D	0.659	neutral	N	0.430398457	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.