TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32471	97636;97637;97638	chr2:178542345;178542344;178542343	chr2:179407072;179407071;179407070
N2AB	30830	92713;92714;92715	chr2:178542345;178542344;178542343	chr2:179407072;179407071;179407070
N2A	29903	89932;89933;89934	chr2:178542345;178542344;178542343	chr2:179407072;179407071;179407070
N2B	23406	70441;70442;70443	chr2:178542345;178542344;178542343	chr2:179407072;179407071;179407070
Novex-1	23531	70816;70817;70818	chr2:178542345;178542344;178542343	chr2:179407072;179407071;179407070
Novex-2	23598	71017;71018;71019	chr2:178542345;178542344;178542343	chr2:179407072;179407071;179407070
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-124
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1083
• 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/A	rs1412547429	None	0.999	N	0.611	0.34	0.658862992856	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs1412547429	None	0.999	N	0.611	0.34	0.658862992856	gnomAD-4.0.0	6.57203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47024E-05	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	0.5859	likely_pathogenic	0.4685	ambiguous	-1.838	Destabilizing	0.999	D	0.611	neutral	N	0.499029036	None	None	N
V/C	0.8598	likely_pathogenic	0.8135	pathogenic	-0.969	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
V/D	0.9555	likely_pathogenic	0.9243	pathogenic	-2.56	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/E	0.8301	likely_pathogenic	0.7724	pathogenic	-2.29	Highly Destabilizing	1.0	D	0.774	deleterious	N	0.441383455	None	None	N
V/F	0.6272	likely_pathogenic	0.4854	ambiguous	-0.984	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
V/G	0.7524	likely_pathogenic	0.6479	pathogenic	-2.377	Highly Destabilizing	1.0	D	0.817	deleterious	N	0.472711911	None	None	N
V/H	0.9523	likely_pathogenic	0.9144	pathogenic	-2.329	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
V/I	0.1037	likely_benign	0.0933	benign	-0.295	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	N
V/K	0.9102	likely_pathogenic	0.8609	pathogenic	-1.216	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/L	0.5258	ambiguous	0.4001	ambiguous	-0.295	Destabilizing	0.997	D	0.621	neutral	N	0.462204231	None	None	N
V/M	0.4166	ambiguous	0.3048	benign	-0.422	Destabilizing	1.0	D	0.682	prob.neutral	N	0.48535045	None	None	N
V/N	0.8594	likely_pathogenic	0.7879	pathogenic	-1.705	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/P	0.9928	likely_pathogenic	0.9883	pathogenic	-0.788	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/Q	0.7724	likely_pathogenic	0.7	pathogenic	-1.423	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/R	0.8608	likely_pathogenic	0.7862	pathogenic	-1.327	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/S	0.6753	likely_pathogenic	0.5722	pathogenic	-2.196	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
V/T	0.5003	ambiguous	0.4304	ambiguous	-1.791	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
V/W	0.9857	likely_pathogenic	0.97	pathogenic	-1.582	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/Y	0.9172	likely_pathogenic	0.8593	pathogenic	-1.174	Destabilizing	1.0	D	0.792	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.