TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16425	49498;49499;49500	chr2:178614124;178614123;178614122	chr2:179478851;179478850;179478849
N2AB	14784	44575;44576;44577	chr2:178614124;178614123;178614122	chr2:179478851;179478850;179478849
N2A	13857	41794;41795;41796	chr2:178614124;178614123;178614122	chr2:179478851;179478850;179478849
N2B	7360	22303;22304;22305	chr2:178614124;178614123;178614122	chr2:179478851;179478850;179478849
Novex-1	7485	22678;22679;22680	chr2:178614124;178614123;178614122	chr2:179478851;179478850;179478849
Novex-2	7552	22879;22880;22881	chr2:178614124;178614123;178614122	chr2:179478851;179478850;179478849
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-6
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0666
• 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	None	None	0.999	D	0.657	0.689	0.810761783182	gnomAD-4.0.0	2.05409E-06	None	None	None	None	N	None	2.99258E-05	0	None	0	0	None	0	0	8.99821E-07	1.15982E-05	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	0.838	likely_pathogenic	0.7854	pathogenic	-2.541	Highly Destabilizing	0.999	D	0.657	neutral	D	0.813382508	None	None	N
V/C	0.979	likely_pathogenic	0.9705	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
V/D	0.9994	likely_pathogenic	0.999	pathogenic	-3.548	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.846972479	None	None	N
V/E	0.998	likely_pathogenic	0.997	pathogenic	-3.246	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/F	0.979	likely_pathogenic	0.968	pathogenic	-1.477	Destabilizing	1.0	D	0.797	deleterious	D	0.845910386	None	None	N
V/G	0.9537	likely_pathogenic	0.9364	pathogenic	-3.09	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.846972479	None	None	N
V/H	0.9996	likely_pathogenic	0.9993	pathogenic	-2.878	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.1559	likely_benign	0.1421	benign	-0.92	Destabilizing	0.997	D	0.607	neutral	D	0.545952137	None	None	N
V/K	0.9987	likely_pathogenic	0.9979	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/L	0.8992	likely_pathogenic	0.8638	pathogenic	-0.92	Destabilizing	0.997	D	0.671	neutral	D	0.654502453	None	None	N
V/M	0.9325	likely_pathogenic	0.9008	pathogenic	-1.211	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/N	0.9977	likely_pathogenic	0.9964	pathogenic	-2.864	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/P	0.9975	likely_pathogenic	0.996	pathogenic	-1.448	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/Q	0.9979	likely_pathogenic	0.9968	pathogenic	-2.544	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/R	0.9968	likely_pathogenic	0.9953	pathogenic	-2.194	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
V/S	0.9797	likely_pathogenic	0.9705	pathogenic	-3.31	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/T	0.925	likely_pathogenic	0.8994	pathogenic	-2.869	Highly Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
V/W	0.9998	likely_pathogenic	0.9996	pathogenic	-1.991	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9983	likely_pathogenic	0.9973	pathogenic	-1.756	Destabilizing	1.0	D	0.803	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.