TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27980	84163;84164;84165	chr2:178562194;178562193;178562192	chr2:179426921;179426920;179426919
N2AB	26339	79240;79241;79242	chr2:178562194;178562193;178562192	chr2:179426921;179426920;179426919
N2A	25412	76459;76460;76461	chr2:178562194;178562193;178562192	chr2:179426921;179426920;179426919
N2B	18915	56968;56969;56970	chr2:178562194;178562193;178562192	chr2:179426921;179426920;179426919
Novex-1	19040	57343;57344;57345	chr2:178562194;178562193;178562192	chr2:179426921;179426920;179426919
Novex-2	19107	57544;57545;57546	chr2:178562194;178562193;178562192	chr2:179426921;179426920;179426919
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-142
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1779
• 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	rs1060500536	None	0.142	N	0.535	0.418	0.728030011221	gnomAD-4.0.0	4.10741E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39806E-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	0.7489	likely_pathogenic	0.7799	pathogenic	-2.047	Highly Destabilizing	0.938	D	0.632	neutral	None	None	None	None	N
L/C	0.7494	likely_pathogenic	0.7903	pathogenic	-1.537	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/D	0.9928	likely_pathogenic	0.9965	pathogenic	-1.425	Destabilizing	0.991	D	0.833	deleterious	None	None	None	None	N
L/E	0.9612	likely_pathogenic	0.9801	pathogenic	-1.264	Destabilizing	0.991	D	0.824	deleterious	None	None	None	None	N
L/F	0.3907	ambiguous	0.4271	ambiguous	-1.103	Destabilizing	0.998	D	0.771	deleterious	N	0.454859648	None	None	N
L/G	0.9389	likely_pathogenic	0.9553	pathogenic	-2.538	Highly Destabilizing	0.991	D	0.823	deleterious	None	None	None	None	N
L/H	0.9106	likely_pathogenic	0.952	pathogenic	-1.74	Destabilizing	0.999	D	0.833	deleterious	N	0.501881485	None	None	N
L/I	0.1388	likely_benign	0.1264	benign	-0.684	Destabilizing	0.979	D	0.581	neutral	N	0.488416893	None	None	N
L/K	0.9295	likely_pathogenic	0.9642	pathogenic	-1.491	Destabilizing	0.991	D	0.8	deleterious	None	None	None	None	N
L/M	0.2115	likely_benign	0.2224	benign	-0.734	Destabilizing	0.998	D	0.752	deleterious	None	None	None	None	N
L/N	0.9658	likely_pathogenic	0.9807	pathogenic	-1.616	Destabilizing	0.995	D	0.849	deleterious	None	None	None	None	N
L/P	0.9719	likely_pathogenic	0.9814	pathogenic	-1.112	Destabilizing	0.142	N	0.535	neutral	N	0.501881485	None	None	N
L/Q	0.8385	likely_pathogenic	0.9132	pathogenic	-1.544	Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	N
L/R	0.8861	likely_pathogenic	0.9407	pathogenic	-1.157	Destabilizing	0.994	D	0.821	deleterious	N	0.490107106	None	None	N
L/S	0.9438	likely_pathogenic	0.9639	pathogenic	-2.419	Highly Destabilizing	0.991	D	0.787	deleterious	None	None	None	None	N
L/T	0.7922	likely_pathogenic	0.8383	pathogenic	-2.105	Highly Destabilizing	0.991	D	0.775	deleterious	None	None	None	None	N
L/V	0.1444	likely_benign	0.1412	benign	-1.112	Destabilizing	0.958	D	0.534	neutral	N	0.47481009	None	None	N
L/W	0.7888	likely_pathogenic	0.853	pathogenic	-1.293	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/Y	0.8444	likely_pathogenic	0.8932	pathogenic	-1.029	Destabilizing	0.998	D	0.826	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.