TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6564	19915;19916;19917	chr2:178728134;178728133;178728132	chr2:179592861;179592860;179592859
N2AB	6247	18964;18965;18966	chr2:178728134;178728133;178728132	chr2:179592861;179592860;179592859
N2A	5320	16183;16184;16185	chr2:178728134;178728133;178728132	chr2:179592861;179592860;179592859
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-49
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.0859
• 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/F	None	None	0.998	N	0.775	0.471	0.781870579539	gnomAD-4.0.0	6.93134E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.20989E-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	0.5533	ambiguous	0.6095	pathogenic	-1.919	Destabilizing	0.864	D	0.555	neutral	None	None	None	None	N
C/D	0.9126	likely_pathogenic	0.9298	pathogenic	-0.459	Destabilizing	0.991	D	0.8	deleterious	None	None	None	None	N
C/E	0.9674	likely_pathogenic	0.9746	pathogenic	-0.353	Destabilizing	0.991	D	0.801	deleterious	None	None	None	None	N
C/F	0.5381	ambiguous	0.5591	ambiguous	-1.291	Destabilizing	0.998	D	0.775	deleterious	N	0.502088745	None	None	N
C/G	0.3765	ambiguous	0.4219	ambiguous	-2.231	Highly Destabilizing	0.03	N	0.549	neutral	N	0.502088745	None	None	N
C/H	0.8765	likely_pathogenic	0.9131	pathogenic	-2.188	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
C/I	0.7519	likely_pathogenic	0.7692	pathogenic	-1.112	Destabilizing	0.995	D	0.794	deleterious	None	None	None	None	N
C/K	0.9788	likely_pathogenic	0.9862	pathogenic	-1.027	Destabilizing	0.991	D	0.799	deleterious	None	None	None	None	N
C/L	0.7728	likely_pathogenic	0.7974	pathogenic	-1.112	Destabilizing	0.984	D	0.719	prob.delet.	None	None	None	None	N
C/M	0.8431	likely_pathogenic	0.861	pathogenic	-0.131	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
C/N	0.8208	likely_pathogenic	0.8587	pathogenic	-1.01	Destabilizing	0.991	D	0.798	deleterious	None	None	None	None	N
C/P	0.9935	likely_pathogenic	0.9947	pathogenic	-1.356	Destabilizing	0.995	D	0.817	deleterious	None	None	None	None	N
C/Q	0.9175	likely_pathogenic	0.941	pathogenic	-0.93	Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	N
C/R	0.8719	likely_pathogenic	0.9109	pathogenic	-0.886	Destabilizing	0.994	D	0.816	deleterious	N	0.493263653	None	None	N
C/S	0.2674	likely_benign	0.3292	benign	-1.589	Destabilizing	0.476	N	0.569	neutral	N	0.477144759	None	None	N
C/T	0.4765	ambiguous	0.53	ambiguous	-1.297	Destabilizing	0.939	D	0.718	prob.delet.	None	None	None	None	N
C/V	0.6006	likely_pathogenic	0.6258	pathogenic	-1.356	Destabilizing	0.984	D	0.754	deleterious	None	None	None	None	N
C/W	0.8773	likely_pathogenic	0.8956	pathogenic	-1.253	Destabilizing	0.999	D	0.751	deleterious	N	0.504988807	None	None	N
C/Y	0.7642	likely_pathogenic	0.8031	pathogenic	-1.255	Destabilizing	0.998	D	0.775	deleterious	N	0.497075542	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.