TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22726	68401;68402;68403	chr2:178578854;178578853;178578852	chr2:179443581;179443580;179443579
N2AB	21085	63478;63479;63480	chr2:178578854;178578853;178578852	chr2:179443581;179443580;179443579
N2A	20158	60697;60698;60699	chr2:178578854;178578853;178578852	chr2:179443581;179443580;179443579
N2B	13661	41206;41207;41208	chr2:178578854;178578853;178578852	chr2:179443581;179443580;179443579
Novex-1	13786	41581;41582;41583	chr2:178578854;178578853;178578852	chr2:179443581;179443580;179443579
Novex-2	13853	41782;41783;41784	chr2:178578854;178578853;178578852	chr2:179443581;179443580;179443579
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-52
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3958
• 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
V/I	rs1553620392	None	0.046	N	0.24	0.05	0.340992353424	gnomAD-4.0.0	1.59279E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86126E-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
V/A	0.2425	likely_benign	0.2593	benign	-0.991	Destabilizing	0.939	D	0.604	neutral	N	0.46143344	None	None	N
V/C	0.7698	likely_pathogenic	0.8142	pathogenic	-0.836	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
V/D	0.7565	likely_pathogenic	0.7777	pathogenic	-0.61	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
V/E	0.5534	ambiguous	0.6161	pathogenic	-0.694	Destabilizing	0.997	D	0.805	deleterious	N	0.478920336	None	None	N
V/F	0.3296	likely_benign	0.3151	benign	-1.022	Destabilizing	0.986	D	0.783	deleterious	None	None	None	None	N
V/G	0.4247	ambiguous	0.466	ambiguous	-1.192	Destabilizing	0.997	D	0.797	deleterious	N	0.466467259	None	None	N
V/H	0.7942	likely_pathogenic	0.8294	pathogenic	-0.611	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
V/I	0.0754	likely_benign	0.0682	benign	-0.584	Destabilizing	0.046	N	0.24	neutral	N	0.429822454	None	None	N
V/K	0.5098	ambiguous	0.6075	pathogenic	-0.653	Destabilizing	0.993	D	0.812	deleterious	None	None	None	None	N
V/L	0.3454	ambiguous	0.3604	ambiguous	-0.584	Destabilizing	0.76	D	0.527	neutral	N	0.465396465	None	None	N
V/M	0.2225	likely_benign	0.2201	benign	-0.454	Destabilizing	0.986	D	0.783	deleterious	None	None	None	None	N
V/N	0.5589	ambiguous	0.5835	pathogenic	-0.385	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
V/P	0.7259	likely_pathogenic	0.6773	pathogenic	-0.684	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
V/Q	0.495	ambiguous	0.5605	ambiguous	-0.675	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
V/R	0.4347	ambiguous	0.5243	ambiguous	-0.071	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
V/S	0.3701	ambiguous	0.4056	ambiguous	-0.873	Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	N
V/T	0.1983	likely_benign	0.2052	benign	-0.853	Destabilizing	0.953	D	0.716	prob.delet.	None	None	None	None	N
V/W	0.9111	likely_pathogenic	0.9102	pathogenic	-1.048	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
V/Y	0.7693	likely_pathogenic	0.7766	pathogenic	-0.763	Destabilizing	0.998	D	0.801	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.