TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9549	28870;28871;28872	chr2:178709674;178709673;178709672	chr2:179574401;179574400;179574399
N2AB	9232	27919;27920;27921	chr2:178709674;178709673;178709672	chr2:179574401;179574400;179574399
N2A	8305	25138;25139;25140	chr2:178709674;178709673;178709672	chr2:179574401;179574400;179574399
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-81
• Domain position: 57
• Structural Position: 136
• Q(SASA): 0.1235
• 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
L/S	rs763448983	-2.729	0.193	None	0.757	0.27	0.557286757043	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
L/S	rs763448983	-2.729	0.193	None	0.757	0.27	0.557286757043	gnomAD-4.0.0	1.59108E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85801E-06	0	0
L/V	None	None	0.001	None	0.438	0.093	0.0920862733494	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	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
L/A	0.3593	ambiguous	0.3882	ambiguous	-2.501	Highly Destabilizing	0.004	N	0.517	neutral	None	None	None	None	N
L/C	0.6741	likely_pathogenic	0.7024	pathogenic	-1.688	Destabilizing	0.981	D	0.738	prob.delet.	None	None	None	None	N
L/D	0.9933	likely_pathogenic	0.9942	pathogenic	-2.945	Highly Destabilizing	0.818	D	0.809	deleterious	None	None	None	None	N
L/E	0.9684	likely_pathogenic	0.9678	pathogenic	-2.629	Highly Destabilizing	0.818	D	0.806	deleterious	None	None	None	None	N
L/F	0.3651	ambiguous	0.3865	ambiguous	-1.463	Destabilizing	0.627	D	0.757	deleterious	None	None	None	None	N
L/G	0.8977	likely_pathogenic	0.9161	pathogenic	-3.127	Highly Destabilizing	0.241	N	0.775	deleterious	None	None	None	None	N
L/H	0.8908	likely_pathogenic	0.8861	pathogenic	-2.742	Highly Destabilizing	0.981	D	0.764	deleterious	None	None	None	None	N
L/I	0.0786	likely_benign	0.0797	benign	-0.641	Destabilizing	0.001	N	0.41	neutral	None	None	None	None	N
L/K	0.9727	likely_pathogenic	0.9733	pathogenic	-1.79	Destabilizing	0.69	D	0.789	deleterious	None	None	None	None	N
L/M	0.1552	likely_benign	0.154	benign	-0.719	Destabilizing	0.69	D	0.727	prob.delet.	None	None	None	None	N
L/N	0.9431	likely_pathogenic	0.9477	pathogenic	-2.409	Highly Destabilizing	0.932	D	0.813	deleterious	None	None	None	None	N
L/P	0.963	likely_pathogenic	0.9688	pathogenic	-1.248	Destabilizing	0.818	D	0.812	deleterious	None	None	None	None	N
L/Q	0.8887	likely_pathogenic	0.8787	pathogenic	-2.087	Highly Destabilizing	0.932	D	0.788	deleterious	None	None	None	None	N
L/R	0.9378	likely_pathogenic	0.9388	pathogenic	-1.837	Destabilizing	0.818	D	0.792	deleterious	None	None	None	None	N
L/S	0.7561	likely_pathogenic	0.7838	pathogenic	-3.082	Highly Destabilizing	0.193	N	0.757	deleterious	None	None	None	None	N
L/T	0.4844	ambiguous	0.4996	ambiguous	-2.592	Highly Destabilizing	0.388	N	0.76	deleterious	None	None	None	None	N
L/V	0.0758	likely_benign	0.0734	benign	-1.248	Destabilizing	0.001	N	0.438	neutral	None	None	None	None	N
L/W	0.8663	likely_pathogenic	0.8649	pathogenic	-1.874	Destabilizing	0.981	D	0.753	deleterious	None	None	None	None	N
L/Y	0.8693	likely_pathogenic	0.8833	pathogenic	-1.577	Destabilizing	0.818	D	0.798	deleterious	None	None	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.