TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13802	41629;41630;41631	chr2:178636167;178636166;178636165	chr2:179500894;179500893;179500892
N2AB	12161	36706;36707;36708	chr2:178636167;178636166;178636165	chr2:179500894;179500893;179500892
N2A	11234	33925;33926;33927	chr2:178636167;178636166;178636165	chr2:179500894;179500893;179500892
N2B	4737	14434;14435;14436	chr2:178636167;178636166;178636165	chr2:179500894;179500893;179500892
Novex-1	4862	14809;14810;14811	chr2:178636167;178636166;178636165	chr2:179500894;179500893;179500892
Novex-2	4929	15010;15011;15012	chr2:178636167;178636166;178636165	chr2:179500894;179500893;179500892
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: Ig-88
• Domain position: 23
• Structural Position: 33
• Q(SASA): 0.1006
• 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	0.998	D	0.813	0.414	0.431035450679	gnomAD-4.0.0	1.59385E-06	None	None	None	None	N	None	0	0	None	0	2.79236E-05	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	0.8884	likely_pathogenic	0.9227	pathogenic	-1.918	Destabilizing	0.927	D	0.636	neutral	None	None	None	None	N
C/D	0.9989	likely_pathogenic	0.9995	pathogenic	-1.801	Destabilizing	0.995	D	0.794	deleterious	None	None	None	None	N
C/E	0.9994	likely_pathogenic	0.9997	pathogenic	-1.547	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
C/F	0.9143	likely_pathogenic	0.9583	pathogenic	-1.17	Destabilizing	0.994	D	0.827	deleterious	D	0.569358689	None	None	N
C/G	0.8241	likely_pathogenic	0.8935	pathogenic	-2.308	Highly Destabilizing	0.068	N	0.595	neutral	D	0.531850176	None	None	N
C/H	0.9973	likely_pathogenic	0.9989	pathogenic	-2.397	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
C/I	0.9225	likely_pathogenic	0.9596	pathogenic	-0.848	Destabilizing	0.939	D	0.78	deleterious	None	None	None	None	N
C/K	0.9996	likely_pathogenic	0.9998	pathogenic	-1.449	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
C/L	0.9197	likely_pathogenic	0.9522	pathogenic	-0.848	Destabilizing	0.939	D	0.803	deleterious	None	None	None	None	N
C/M	0.9648	likely_pathogenic	0.9791	pathogenic	0.259	Stabilizing	0.995	D	0.76	deleterious	None	None	None	None	N
C/N	0.995	likely_pathogenic	0.9974	pathogenic	-2.155	Highly Destabilizing	0.995	D	0.829	deleterious	None	None	None	None	N
C/P	0.999	likely_pathogenic	0.9995	pathogenic	-1.183	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
C/Q	0.9983	likely_pathogenic	0.9992	pathogenic	-1.655	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
C/R	0.9947	likely_pathogenic	0.9978	pathogenic	-1.794	Destabilizing	0.998	D	0.843	deleterious	D	0.569542138	None	None	N
C/S	0.9114	likely_pathogenic	0.9482	pathogenic	-2.491	Highly Destabilizing	0.959	D	0.777	deleterious	D	0.569358689	None	None	N
C/T	0.9219	likely_pathogenic	0.9548	pathogenic	-2.039	Highly Destabilizing	0.969	D	0.771	deleterious	None	None	None	None	N
C/V	0.779	likely_pathogenic	0.8534	pathogenic	-1.183	Destabilizing	0.293	N	0.564	neutral	None	None	None	None	N
C/W	0.9907	likely_pathogenic	0.9962	pathogenic	-1.531	Destabilizing	1.0	D	0.803	deleterious	D	0.569542138	None	None	N
C/Y	0.9853	likely_pathogenic	0.9942	pathogenic	-1.393	Destabilizing	0.998	D	0.813	deleterious	D	0.569542138	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.