TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32493	97702;97703;97704	chr2:178542279;178542278;178542277	chr2:179407006;179407005;179407004
N2AB	30852	92779;92780;92781	chr2:178542279;178542278;178542277	chr2:179407006;179407005;179407004
N2A	29925	89998;89999;90000	chr2:178542279;178542278;178542277	chr2:179407006;179407005;179407004
N2B	23428	70507;70508;70509	chr2:178542279;178542278;178542277	chr2:179407006;179407005;179407004
Novex-1	23553	70882;70883;70884	chr2:178542279;178542278;178542277	chr2:179407006;179407005;179407004
Novex-2	23620	71083;71084;71085	chr2:178542279;178542278;178542277	chr2:179407006;179407005;179407004
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: Fn3-124
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.324
• 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/G	None	None	0.999	N	0.813	0.507	0.86908709854	gnomAD-4.0.0	1.60681E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.04599E-05

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	0.6281	likely_pathogenic	0.5647	pathogenic	-1.443	Destabilizing	0.995	D	0.597	neutral	None	None	None	None	N
C/D	0.9966	likely_pathogenic	0.9946	pathogenic	-1.837	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
C/E	0.9975	likely_pathogenic	0.9959	pathogenic	-1.637	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
C/F	0.8932	likely_pathogenic	0.8165	pathogenic	-1.208	Destabilizing	0.999	D	0.885	deleterious	N	0.48421739	None	None	N
C/G	0.684	likely_pathogenic	0.5701	pathogenic	-1.687	Destabilizing	0.999	D	0.813	deleterious	N	0.48447088	None	None	N
C/H	0.9913	likely_pathogenic	0.9853	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
C/I	0.7677	likely_pathogenic	0.6923	pathogenic	-0.804	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
C/K	0.9978	likely_pathogenic	0.9962	pathogenic	-1.073	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
C/L	0.7749	likely_pathogenic	0.7386	pathogenic	-0.804	Destabilizing	0.998	D	0.649	prob.neutral	None	None	None	None	N
C/M	0.9051	likely_pathogenic	0.8884	pathogenic	-0.967	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
C/N	0.9709	likely_pathogenic	0.957	pathogenic	-1.53	Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
C/P	0.9742	likely_pathogenic	0.9625	pathogenic	-0.999	Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
C/Q	0.9914	likely_pathogenic	0.9869	pathogenic	-1.15	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
C/R	0.9856	likely_pathogenic	0.9753	pathogenic	-1.5	Destabilizing	0.999	D	0.884	deleterious	N	0.485484838	None	None	N
C/S	0.8032	likely_pathogenic	0.734	pathogenic	-1.705	Destabilizing	0.999	D	0.813	deleterious	N	0.483963901	None	None	N
C/T	0.8671	likely_pathogenic	0.8234	pathogenic	-1.373	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
C/V	0.616	likely_pathogenic	0.5569	ambiguous	-0.999	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
C/W	0.9873	likely_pathogenic	0.9743	pathogenic	-1.72	Destabilizing	1.0	D	0.858	deleterious	N	0.485738328	None	None	N
C/Y	0.9546	likely_pathogenic	0.915	pathogenic	-1.388	Destabilizing	0.999	D	0.896	deleterious	N	0.484977859	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.