TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6538	19837;19838;19839	chr2:178728212;178728211;178728210	chr2:179592939;179592938;179592937
N2AB	6221	18886;18887;18888	chr2:178728212;178728211;178728210	chr2:179592939;179592938;179592937
N2A	5294	16105;16106;16107	chr2:178728212;178728211;178728210	chr2:179592939;179592938;179592937
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-49
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0529
• 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/P	rs1376037086	None	1.0	D	0.894	0.851	0.919609823937	gnomAD-4.0.0	4.77943E-06	None	None	None	None	N	None	0	0	None	0	5.55494E-05	None	0	0	0	0	3.02828E-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
L/A	0.8228	likely_pathogenic	0.8809	pathogenic	-2.758	Highly Destabilizing	0.997	D	0.778	deleterious	None	None	None	None	N
L/C	0.8665	likely_pathogenic	0.901	pathogenic	-1.995	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/D	0.9982	likely_pathogenic	0.9989	pathogenic	-3.479	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/E	0.985	likely_pathogenic	0.99	pathogenic	-3.172	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
L/F	0.3467	ambiguous	0.3947	ambiguous	-1.609	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
L/G	0.965	likely_pathogenic	0.9753	pathogenic	-3.318	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/H	0.9588	likely_pathogenic	0.9731	pathogenic	-3.009	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/I	0.2165	likely_benign	0.301	benign	-1.053	Destabilizing	0.985	D	0.705	prob.neutral	None	None	None	None	N
L/K	0.9713	likely_pathogenic	0.9787	pathogenic	-2.117	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/M	0.1716	likely_benign	0.1822	benign	-1.353	Destabilizing	0.999	D	0.758	deleterious	D	0.538828504	None	None	N
L/N	0.9905	likely_pathogenic	0.9944	pathogenic	-2.839	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/P	0.9889	likely_pathogenic	0.9937	pathogenic	-1.617	Destabilizing	1.0	D	0.894	deleterious	D	0.581166306	None	None	N
L/Q	0.9219	likely_pathogenic	0.9445	pathogenic	-2.489	Highly Destabilizing	1.0	D	0.9	deleterious	D	0.569810001	None	None	N
L/R	0.9404	likely_pathogenic	0.9571	pathogenic	-2.199	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.581166306	None	None	N
L/S	0.9616	likely_pathogenic	0.9774	pathogenic	-3.298	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/T	0.9072	likely_pathogenic	0.9462	pathogenic	-2.84	Highly Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
L/V	0.2219	likely_benign	0.2958	benign	-1.617	Destabilizing	0.767	D	0.417	neutral	D	0.54318337	None	None	N
L/W	0.8019	likely_pathogenic	0.8538	pathogenic	-1.967	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/Y	0.9026	likely_pathogenic	0.9268	pathogenic	-1.844	Destabilizing	1.0	D	0.827	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.