TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30390	91393;91394;91395	chr2:178551732;178551731;178551730	chr2:179416459;179416458;179416457
N2AB	28749	86470;86471;86472	chr2:178551732;178551731;178551730	chr2:179416459;179416458;179416457
N2A	27822	83689;83690;83691	chr2:178551732;178551731;178551730	chr2:179416459;179416458;179416457
N2B	21325	64198;64199;64200	chr2:178551732;178551731;178551730	chr2:179416459;179416458;179416457
Novex-1	21450	64573;64574;64575	chr2:178551732;178551731;178551730	chr2:179416459;179416458;179416457
Novex-2	21517	64774;64775;64776	chr2:178551732;178551731;178551730	chr2:179416459;179416458;179416457
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: Fn3-109
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.4214
• 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/E	rs779492740	-0.247	0.106	N	0.387	0.28	0.572487460518	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
V/E	rs779492740	-0.247	0.106	N	0.387	0.28	0.572487460518	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	None	0	0	0	0	0
V/I	None	None	None	N	0.077	0.053	0.154104182512	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.141	likely_benign	0.1552	benign	-1.049	Destabilizing	0.005	N	0.173	neutral	N	0.473111871	None	None	N
V/C	0.5752	likely_pathogenic	0.6233	pathogenic	-0.88	Destabilizing	0.628	D	0.368	neutral	None	None	None	None	N
V/D	0.4586	ambiguous	0.5227	ambiguous	-0.384	Destabilizing	0.356	N	0.411	neutral	None	None	None	None	N
V/E	0.3218	likely_benign	0.354	ambiguous	-0.4	Destabilizing	0.106	N	0.387	neutral	N	0.424509848	None	None	N
V/F	0.1468	likely_benign	0.183	benign	-0.793	Destabilizing	0.038	N	0.319	neutral	None	None	None	None	N
V/G	0.2404	likely_benign	0.2833	benign	-1.321	Destabilizing	0.055	N	0.347	neutral	N	0.483877179	None	None	N
V/H	0.4557	ambiguous	0.4999	ambiguous	-0.655	Destabilizing	0.628	D	0.343	neutral	None	None	None	None	N
V/I	0.061	likely_benign	0.0603	benign	-0.427	Destabilizing	None	N	0.077	neutral	N	0.395960597	None	None	N
V/K	0.3757	ambiguous	0.3904	ambiguous	-0.774	Destabilizing	0.072	N	0.339	neutral	None	None	None	None	N
V/L	0.0803	likely_benign	0.0882	benign	-0.427	Destabilizing	None	N	0.07	neutral	N	0.466569901	None	None	N
V/M	0.0743	likely_benign	0.0899	benign	-0.493	Destabilizing	None	N	0.079	neutral	None	None	None	None	N
V/N	0.2215	likely_benign	0.2592	benign	-0.643	Destabilizing	0.356	N	0.401	neutral	None	None	None	None	N
V/P	0.6365	likely_pathogenic	0.6939	pathogenic	-0.598	Destabilizing	0.628	D	0.408	neutral	None	None	None	None	N
V/Q	0.248	likely_benign	0.2678	benign	-0.774	Destabilizing	0.214	N	0.403	neutral	None	None	None	None	N
V/R	0.3142	likely_benign	0.3352	benign	-0.291	Destabilizing	0.214	N	0.413	neutral	None	None	None	None	N
V/S	0.163	likely_benign	0.1916	benign	-1.199	Destabilizing	0.072	N	0.313	neutral	None	None	None	None	N
V/T	0.111	likely_benign	0.1195	benign	-1.091	Destabilizing	0.031	N	0.129	neutral	None	None	None	None	N
V/W	0.6199	likely_pathogenic	0.7003	pathogenic	-0.907	Destabilizing	0.864	D	0.339	neutral	None	None	None	None	N
V/Y	0.4087	ambiguous	0.4967	ambiguous	-0.608	Destabilizing	0.136	N	0.419	neutral	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.