TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31420	94483;94484;94485	chr2:178547267;178547266;178547265	chr2:179411994;179411993;179411992
N2AB	29779	89560;89561;89562	chr2:178547267;178547266;178547265	chr2:179411994;179411993;179411992
N2A	28852	86779;86780;86781	chr2:178547267;178547266;178547265	chr2:179411994;179411993;179411992
N2B	22355	67288;67289;67290	chr2:178547267;178547266;178547265	chr2:179411994;179411993;179411992
Novex-1	22480	67663;67664;67665	chr2:178547267;178547266;178547265	chr2:179411994;179411993;179411992
Novex-2	22547	67864;67865;67866	chr2:178547267;178547266;178547265	chr2:179411994;179411993;179411992
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: Fn3-117
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2956
• 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/M	rs1697609809	None	0.83	N	0.7	0.315	0.627153701111	gnomAD-4.0.0	6.84396E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99719E-07	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	0.3028	likely_benign	0.3259	benign	-1.548	Destabilizing	0.581	D	0.482	neutral	N	0.514654637	None	None	N
V/C	0.6948	likely_pathogenic	0.7129	pathogenic	-1.274	Destabilizing	0.993	D	0.759	deleterious	None	None	None	None	N
V/D	0.8579	likely_pathogenic	0.8966	pathogenic	-2.062	Highly Destabilizing	0.929	D	0.844	deleterious	None	None	None	None	N
V/E	0.7259	likely_pathogenic	0.7811	pathogenic	-2.066	Highly Destabilizing	0.908	D	0.816	deleterious	N	0.513683815	None	None	N
V/F	0.349	ambiguous	0.3949	ambiguous	-1.45	Destabilizing	0.866	D	0.812	deleterious	None	None	None	None	N
V/G	0.4978	ambiguous	0.5489	ambiguous	-1.864	Destabilizing	0.908	D	0.827	deleterious	N	0.503848447	None	None	N
V/H	0.8322	likely_pathogenic	0.8719	pathogenic	-1.574	Destabilizing	0.993	D	0.834	deleterious	None	None	None	None	N
V/I	0.0749	likely_benign	0.0765	benign	-0.768	Destabilizing	0.006	N	0.26	neutral	None	None	None	None	N
V/K	0.7171	likely_pathogenic	0.7671	pathogenic	-1.277	Destabilizing	0.929	D	0.813	deleterious	None	None	None	None	N
V/L	0.3764	ambiguous	0.3702	ambiguous	-0.768	Destabilizing	0.09	N	0.385	neutral	N	0.479334956	None	None	N
V/M	0.2496	likely_benign	0.2739	benign	-0.556	Destabilizing	0.83	D	0.7	prob.neutral	N	0.496758103	None	None	N
V/N	0.6404	likely_pathogenic	0.6926	pathogenic	-1.172	Destabilizing	0.976	D	0.842	deleterious	None	None	None	None	N
V/P	0.8382	likely_pathogenic	0.8421	pathogenic	-0.995	Destabilizing	0.976	D	0.826	deleterious	None	None	None	None	N
V/Q	0.6173	likely_pathogenic	0.6646	pathogenic	-1.383	Destabilizing	0.976	D	0.82	deleterious	None	None	None	None	N
V/R	0.6322	likely_pathogenic	0.6939	pathogenic	-0.786	Destabilizing	0.929	D	0.841	deleterious	None	None	None	None	N
V/S	0.4077	ambiguous	0.4551	ambiguous	-1.62	Destabilizing	0.929	D	0.811	deleterious	None	None	None	None	N
V/T	0.2892	likely_benign	0.3084	benign	-1.516	Destabilizing	0.648	D	0.59	neutral	None	None	None	None	N
V/W	0.9378	likely_pathogenic	0.952	pathogenic	-1.704	Destabilizing	0.993	D	0.828	deleterious	None	None	None	None	N
V/Y	0.7651	likely_pathogenic	0.8085	pathogenic	-1.37	Destabilizing	0.929	D	0.821	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.