TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15674	47245;47246;47247	chr2:178618438;178618437;178618436	chr2:179483165;179483164;179483163
N2AB	14033	42322;42323;42324	chr2:178618438;178618437;178618436	chr2:179483165;179483164;179483163
N2A	13106	39541;39542;39543	chr2:178618438;178618437;178618436	chr2:179483165;179483164;179483163
N2B	6609	20050;20051;20052	chr2:178618438;178618437;178618436	chr2:179483165;179483164;179483163
Novex-1	6734	20425;20426;20427	chr2:178618438;178618437;178618436	chr2:179483165;179483164;179483163
Novex-2	6801	20626;20627;20628	chr2:178618438;178618437;178618436	chr2:179483165;179483164;179483163
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: Fn3-1
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0902
• 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	rs1390266965	-0.712	0.349	N	0.517	0.165	0.264547087235	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.87687E-04	0	0
V/L	rs1390266965	-0.712	0.349	N	0.517	0.165	0.264547087235	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.42E-05	0	0	0	0
V/L	rs1390266965	-0.712	0.349	N	0.517	0.165	0.264547087235	gnomAD-4.0.0	6.58129E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.4162E-05	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	0.7437	likely_pathogenic	0.6412	pathogenic	-2.276	Highly Destabilizing	0.008	N	0.37	neutral	N	0.483902948	None	None	N
V/C	0.9132	likely_pathogenic	0.8635	pathogenic	-2.241	Highly Destabilizing	0.989	D	0.785	deleterious	None	None	None	None	N
V/D	0.9982	likely_pathogenic	0.9927	pathogenic	-2.989	Highly Destabilizing	0.961	D	0.879	deleterious	None	None	None	None	N
V/E	0.9932	likely_pathogenic	0.9804	pathogenic	-2.697	Highly Destabilizing	0.901	D	0.869	deleterious	D	0.701761942	None	None	N
V/F	0.9082	likely_pathogenic	0.8297	pathogenic	-1.321	Destabilizing	0.961	D	0.844	deleterious	None	None	None	None	N
V/G	0.9234	likely_pathogenic	0.8381	pathogenic	-2.878	Highly Destabilizing	0.82	D	0.84	deleterious	D	0.701761942	None	None	N
V/H	0.9981	likely_pathogenic	0.9949	pathogenic	-2.69	Highly Destabilizing	0.996	D	0.841	deleterious	None	None	None	None	N
V/I	0.1211	likely_benign	0.1251	benign	-0.551	Destabilizing	0.044	N	0.244	neutral	None	None	None	None	N
V/K	0.9951	likely_pathogenic	0.9875	pathogenic	-1.776	Destabilizing	0.923	D	0.869	deleterious	None	None	None	None	N
V/L	0.7377	likely_pathogenic	0.6914	pathogenic	-0.551	Destabilizing	0.349	N	0.517	neutral	N	0.479057069	None	None	N
V/M	0.7167	likely_pathogenic	0.6418	pathogenic	-1.031	Destabilizing	0.949	D	0.692	prob.neutral	D	0.576582037	None	None	N
V/N	0.9913	likely_pathogenic	0.9753	pathogenic	-2.349	Highly Destabilizing	0.961	D	0.873	deleterious	None	None	None	None	N
V/P	0.9981	likely_pathogenic	0.9951	pathogenic	-1.103	Destabilizing	0.961	D	0.857	deleterious	None	None	None	None	N
V/Q	0.9919	likely_pathogenic	0.9781	pathogenic	-2.051	Highly Destabilizing	0.961	D	0.853	deleterious	None	None	None	None	N
V/R	0.991	likely_pathogenic	0.9778	pathogenic	-1.835	Destabilizing	0.923	D	0.871	deleterious	None	None	None	None	N
V/S	0.9649	likely_pathogenic	0.9114	pathogenic	-2.986	Highly Destabilizing	0.858	D	0.847	deleterious	None	None	None	None	N
V/T	0.8589	likely_pathogenic	0.7909	pathogenic	-2.524	Highly Destabilizing	0.775	D	0.705	prob.neutral	None	None	None	None	N
V/W	0.999	likely_pathogenic	0.9973	pathogenic	-1.801	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
V/Y	0.9891	likely_pathogenic	0.9746	pathogenic	-1.466	Destabilizing	0.987	D	0.817	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.