TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21428	64507;64508;64509	chr2:178586619;178586618;178586617	chr2:179451346;179451345;179451344
N2AB	19787	59584;59585;59586	chr2:178586619;178586618;178586617	chr2:179451346;179451345;179451344
N2A	18860	56803;56804;56805	chr2:178586619;178586618;178586617	chr2:179451346;179451345;179451344
N2B	12363	37312;37313;37314	chr2:178586619;178586618;178586617	chr2:179451346;179451345;179451344
Novex-1	12488	37687;37688;37689	chr2:178586619;178586618;178586617	chr2:179451346;179451345;179451344
Novex-2	12555	37888;37889;37890	chr2:178586619;178586618;178586617	chr2:179451346;179451345;179451344
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-43
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.0812
• 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	rs1576014979	None	0.958	N	0.641	0.374	0.6554178980150001	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs1576014979	None	0.958	N	0.641	0.374	0.6554178980150001	gnomAD-4.0.0	2.56421E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.39501E-06	0	2.84657E-05
V/F	None	None	0.988	N	0.791	0.366	0.715876910944	gnomAD-4.0.0	1.59263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86089E-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	0.7751	likely_pathogenic	0.731	pathogenic	-1.241	Destabilizing	0.958	D	0.641	neutral	N	0.479809618	None	None	N
V/C	0.949	likely_pathogenic	0.9365	pathogenic	-0.809	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/D	0.9946	likely_pathogenic	0.9913	pathogenic	-1.403	Destabilizing	0.998	D	0.808	deleterious	N	0.495445111	None	None	N
V/E	0.9806	likely_pathogenic	0.9697	pathogenic	-1.122	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
V/F	0.6492	likely_pathogenic	0.568	pathogenic	-0.667	Destabilizing	0.988	D	0.791	deleterious	N	0.50129078	None	None	N
V/G	0.9229	likely_pathogenic	0.9009	pathogenic	-1.811	Destabilizing	0.994	D	0.809	deleterious	D	0.525666139	None	None	N
V/H	0.9901	likely_pathogenic	0.9848	pathogenic	-1.781	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/I	0.0865	likely_benign	0.0857	benign	0.367	Stabilizing	0.067	N	0.259	neutral	N	0.458819997	None	None	N
V/K	0.9772	likely_pathogenic	0.9632	pathogenic	-0.726	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
V/L	0.4503	ambiguous	0.4107	ambiguous	0.367	Stabilizing	0.618	D	0.638	neutral	N	0.505722935	None	None	N
V/M	0.5484	ambiguous	0.4908	ambiguous	0.105	Stabilizing	0.991	D	0.767	deleterious	None	None	None	None	N
V/N	0.9823	likely_pathogenic	0.9742	pathogenic	-1.215	Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	N
V/P	0.9847	likely_pathogenic	0.9824	pathogenic	-0.143	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
V/Q	0.9726	likely_pathogenic	0.9596	pathogenic	-0.847	Destabilizing	0.998	D	0.856	deleterious	None	None	None	None	N
V/R	0.9677	likely_pathogenic	0.9497	pathogenic	-1.081	Destabilizing	0.998	D	0.858	deleterious	None	None	None	None	N
V/S	0.9522	likely_pathogenic	0.9345	pathogenic	-1.863	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
V/T	0.8889	likely_pathogenic	0.8673	pathogenic	-1.399	Destabilizing	0.968	D	0.689	prob.neutral	None	None	None	None	N
V/W	0.9911	likely_pathogenic	0.9867	pathogenic	-1.137	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/Y	0.9644	likely_pathogenic	0.9446	pathogenic	-0.658	Destabilizing	0.995	D	0.79	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.