TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5567	16924;16925;16926	chr2:178732270;178732269;178732268	chr2:179596997;179596996;179596995
N2AB	5250	15973;15974;15975	chr2:178732270;178732269;178732268	chr2:179596997;179596996;179596995
N2A	4323	13192;13193;13194	chr2:178732270;178732269;178732268	chr2:179596997;179596996;179596995
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-39
• Domain position: 25
• Structural Position: 35
• Q(SASA): 0.1017
• 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/L	None	None	0.026	D	0.302	0.354	0.508398094826	gnomAD-4.0.0	1.59152E-06	None	None	None	None	N	None	0	0	None	0	2.77346E-05	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
V/A	0.5884	likely_pathogenic	0.624	pathogenic	-1.7	Destabilizing	0.103	N	0.367	neutral	N	0.484121952	None	None	N
V/C	0.9527	likely_pathogenic	0.9588	pathogenic	-1.479	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
V/D	0.9869	likely_pathogenic	0.989	pathogenic	-1.362	Destabilizing	0.988	D	0.821	deleterious	None	None	None	None	N
V/E	0.9638	likely_pathogenic	0.9698	pathogenic	-1.147	Destabilizing	0.984	D	0.781	deleterious	D	0.55024408	None	None	N
V/F	0.5357	ambiguous	0.5582	ambiguous	-0.944	Destabilizing	0.976	D	0.791	deleterious	None	None	None	None	N
V/G	0.7542	likely_pathogenic	0.7848	pathogenic	-2.233	Highly Destabilizing	0.968	D	0.777	deleterious	D	0.581354144	None	None	N
V/H	0.9875	likely_pathogenic	0.9892	pathogenic	-1.889	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/I	0.1087	likely_benign	0.1164	benign	-0.226	Destabilizing	0.026	N	0.311	neutral	N	0.475499682	None	None	N
V/K	0.9758	likely_pathogenic	0.9797	pathogenic	-1.055	Destabilizing	0.988	D	0.78	deleterious	None	None	None	None	N
V/L	0.4979	ambiguous	0.5167	ambiguous	-0.226	Destabilizing	0.026	N	0.302	neutral	D	0.54285589	None	None	N
V/M	0.466	ambiguous	0.512	ambiguous	-0.522	Destabilizing	0.976	D	0.713	prob.delet.	None	None	None	None	N
V/N	0.9629	likely_pathogenic	0.9708	pathogenic	-1.29	Destabilizing	0.996	D	0.804	deleterious	None	None	None	None	N
V/P	0.9738	likely_pathogenic	0.9773	pathogenic	-0.688	Destabilizing	0.988	D	0.786	deleterious	None	None	None	None	N
V/Q	0.9667	likely_pathogenic	0.9721	pathogenic	-1.1	Destabilizing	0.996	D	0.774	deleterious	None	None	None	None	N
V/R	0.9596	likely_pathogenic	0.9631	pathogenic	-1.09	Destabilizing	0.988	D	0.813	deleterious	None	None	None	None	N
V/S	0.8776	likely_pathogenic	0.9037	pathogenic	-2.082	Highly Destabilizing	0.952	D	0.756	deleterious	None	None	None	None	N
V/T	0.7596	likely_pathogenic	0.8057	pathogenic	-1.704	Destabilizing	0.919	D	0.699	prob.neutral	None	None	None	None	N
V/W	0.9823	likely_pathogenic	0.9855	pathogenic	-1.283	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
V/Y	0.9058	likely_pathogenic	0.9113	pathogenic	-0.899	Destabilizing	0.996	D	0.766	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.