TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27260	82003;82004;82005	chr2:178564354;178564353;178564352	chr2:179429081;179429080;179429079
N2AB	25619	77080;77081;77082	chr2:178564354;178564353;178564352	chr2:179429081;179429080;179429079
N2A	24692	74299;74300;74301	chr2:178564354;178564353;178564352	chr2:179429081;179429080;179429079
N2B	18195	54808;54809;54810	chr2:178564354;178564353;178564352	chr2:179429081;179429080;179429079
Novex-1	18320	55183;55184;55185	chr2:178564354;178564353;178564352	chr2:179429081;179429080;179429079
Novex-2	18387	55384;55385;55386	chr2:178564354;178564353;178564352	chr2:179429081;179429080;179429079
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-86
• Domain position: 91
• Structural Position: 123
• Q(SASA): 0.272
• 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
S/T	rs752173731	-0.581	0.792	N	0.712	0.129	0.128392430309	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
S/T	rs752173731	-0.581	0.792	N	0.712	0.129	0.128392430309	gnomAD-4.0.0	3.18286E-06	None	None	None	None	N	None	0	4.57415E-05	None	0	0	None	0	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
S/A	0.1343	likely_benign	0.1264	benign	-1.02	Destabilizing	0.511	D	0.503	neutral	None	None	None	None	N
S/C	0.1593	likely_benign	0.1593	benign	-0.781	Destabilizing	0.997	D	0.64	neutral	N	0.475555386	None	None	N
S/D	0.6965	likely_pathogenic	0.6674	pathogenic	-0.696	Destabilizing	0.991	D	0.659	prob.neutral	None	None	None	None	N
S/E	0.8307	likely_pathogenic	0.8094	pathogenic	-0.7	Destabilizing	0.911	D	0.684	prob.delet.	None	None	None	None	N
S/F	0.5869	likely_pathogenic	0.5209	ambiguous	-1.257	Destabilizing	0.947	D	0.675	prob.neutral	None	None	None	None	N
S/G	0.1459	likely_benign	0.1511	benign	-1.248	Destabilizing	0.886	D	0.64	neutral	N	0.493406151	None	None	N
S/H	0.6629	likely_pathogenic	0.6239	pathogenic	-1.654	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	N
S/I	0.2783	likely_benign	0.2528	benign	-0.514	Destabilizing	0.657	D	0.671	prob.neutral	N	0.496041872	None	None	N
S/K	0.9045	likely_pathogenic	0.8788	pathogenic	-0.843	Destabilizing	0.911	D	0.67	prob.neutral	None	None	None	None	N
S/L	0.2475	likely_benign	0.2178	benign	-0.514	Destabilizing	0.717	D	0.643	neutral	None	None	None	None	N
S/M	0.4401	ambiguous	0.4163	ambiguous	-0.124	Destabilizing	0.993	D	0.613	neutral	None	None	None	None	N
S/N	0.268	likely_benign	0.2595	benign	-0.833	Destabilizing	0.988	D	0.655	prob.neutral	N	0.475048407	None	None	N
S/P	0.1884	likely_benign	0.1698	benign	-0.652	Destabilizing	0.991	D	0.622	neutral	None	None	None	None	N
S/Q	0.8085	likely_pathogenic	0.7853	pathogenic	-1.08	Destabilizing	0.991	D	0.629	neutral	None	None	None	None	N
S/R	0.8778	likely_pathogenic	0.8391	pathogenic	-0.627	Destabilizing	0.964	D	0.628	neutral	N	0.499229048	None	None	N
S/T	0.1075	likely_benign	0.105	benign	-0.87	Destabilizing	0.792	D	0.712	prob.delet.	N	0.464969604	None	None	N
S/V	0.2768	likely_benign	0.2557	benign	-0.652	Destabilizing	0.016	N	0.619	neutral	None	None	None	None	N
S/W	0.7942	likely_pathogenic	0.7529	pathogenic	-1.165	Destabilizing	0.998	D	0.697	prob.delet.	None	None	None	None	N
S/Y	0.5604	ambiguous	0.503	ambiguous	-0.926	Destabilizing	0.973	D	0.679	prob.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.