TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6844	20755;20756;20757	chr2:178725792;178725791;178725790	chr2:179590519;179590518;179590517
N2AB	6527	19804;19805;19806	chr2:178725792;178725791;178725790	chr2:179590519;179590518;179590517
N2A	5600	17023;17024;17025	chr2:178725792;178725791;178725790	chr2:179590519;179590518;179590517
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: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-52
• Domain position: 84
• Structural Position: 169
• 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/W	None	None	1.0	N	0.745	0.486	0.716924671941	gnomAD-4.0.0	1.61345E-06	None	None	None	None	N	None	0	2.31932E-05	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	0.5201	ambiguous	0.4203	ambiguous	-2.445	Highly Destabilizing	0.926	D	0.511	neutral	None	None	None	None	N
C/D	0.9576	likely_pathogenic	0.9426	pathogenic	-1.341	Destabilizing	0.964	D	0.801	deleterious	None	None	None	None	N
C/E	0.9712	likely_pathogenic	0.9641	pathogenic	-1.166	Destabilizing	0.997	D	0.807	deleterious	None	None	None	None	N
C/F	0.5027	ambiguous	0.4577	ambiguous	-1.564	Destabilizing	1.0	D	0.798	deleterious	N	0.503240834	None	None	N
C/G	0.414	ambiguous	0.3515	ambiguous	-2.787	Highly Destabilizing	0.971	D	0.779	deleterious	D	0.532827471	None	None	N
C/H	0.8467	likely_pathogenic	0.8023	pathogenic	-2.543	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
C/I	0.7356	likely_pathogenic	0.6894	pathogenic	-1.504	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
C/K	0.9513	likely_pathogenic	0.9375	pathogenic	-1.753	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
C/L	0.6898	likely_pathogenic	0.6565	pathogenic	-1.504	Destabilizing	0.995	D	0.756	deleterious	None	None	None	None	N
C/M	0.8028	likely_pathogenic	0.766	pathogenic	0.044	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
C/N	0.8829	likely_pathogenic	0.8163	pathogenic	-1.99	Destabilizing	0.995	D	0.805	deleterious	None	None	None	None	N
C/P	0.9944	likely_pathogenic	0.9953	pathogenic	-1.798	Destabilizing	0.995	D	0.812	deleterious	None	None	None	None	N
C/Q	0.908	likely_pathogenic	0.8732	pathogenic	-1.734	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
C/R	0.7577	likely_pathogenic	0.7202	pathogenic	-1.655	Destabilizing	0.999	D	0.815	deleterious	D	0.530691243	None	None	N
C/S	0.5433	ambiguous	0.3726	ambiguous	-2.522	Highly Destabilizing	0.428	N	0.423	neutral	N	0.474989888	None	None	N
C/T	0.7097	likely_pathogenic	0.5705	pathogenic	-2.172	Highly Destabilizing	0.438	N	0.444	neutral	None	None	None	None	N
C/V	0.6162	likely_pathogenic	0.5503	ambiguous	-1.798	Destabilizing	0.988	D	0.769	deleterious	None	None	None	None	N
C/W	0.8574	likely_pathogenic	0.8404	pathogenic	-1.634	Destabilizing	1.0	D	0.745	deleterious	N	0.515357608	None	None	N
C/Y	0.7009	likely_pathogenic	0.6759	pathogenic	-1.689	Destabilizing	1.0	D	0.775	deleterious	D	0.526371518	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.