TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17057	51394;51395;51396	chr2:178610357;178610356;178610355	chr2:179475084;179475083;179475082
N2AB	15416	46471;46472;46473	chr2:178610357;178610356;178610355	chr2:179475084;179475083;179475082
N2A	14489	43690;43691;43692	chr2:178610357;178610356;178610355	chr2:179475084;179475083;179475082
N2B	7992	24199;24200;24201	chr2:178610357;178610356;178610355	chr2:179475084;179475083;179475082
Novex-1	8117	24574;24575;24576	chr2:178610357;178610356;178610355	chr2:179475084;179475083;179475082
Novex-2	8184	24775;24776;24777	chr2:178610357;178610356;178610355	chr2:179475084;179475083;179475082
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: Fn3-12
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.36
• 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/N	None	None	0.026	N	0.28	0.185	0.149567049428	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0964	likely_benign	0.0874	benign	-0.469	Destabilizing	0.825	D	0.517	neutral	None	None	None	None	N
S/C	0.1655	likely_benign	0.1579	benign	-0.331	Destabilizing	0.999	D	0.65	neutral	N	0.515839504	None	None	N
S/D	0.5888	likely_pathogenic	0.582	pathogenic	-0.152	Destabilizing	0.851	D	0.539	neutral	None	None	None	None	N
S/E	0.6353	likely_pathogenic	0.6066	pathogenic	-0.227	Destabilizing	0.919	D	0.537	neutral	None	None	None	None	N
S/F	0.279	likely_benign	0.2634	benign	-0.91	Destabilizing	0.996	D	0.729	prob.delet.	None	None	None	None	N
S/G	0.1097	likely_benign	0.1029	benign	-0.629	Destabilizing	0.811	D	0.555	neutral	N	0.490082024	None	None	N
S/H	0.475	ambiguous	0.465	ambiguous	-1.159	Destabilizing	0.997	D	0.655	neutral	None	None	None	None	N
S/I	0.2314	likely_benign	0.2149	benign	-0.172	Destabilizing	0.968	D	0.725	prob.delet.	N	0.478464341	None	None	N
S/K	0.8266	likely_pathogenic	0.8106	pathogenic	-0.707	Destabilizing	0.919	D	0.543	neutral	None	None	None	None	N
S/L	0.1378	likely_benign	0.1291	benign	-0.172	Destabilizing	0.919	D	0.608	neutral	None	None	None	None	N
S/M	0.1967	likely_benign	0.1829	benign	0.127	Stabilizing	0.999	D	0.632	neutral	None	None	None	None	N
S/N	0.1778	likely_benign	0.1739	benign	-0.464	Destabilizing	0.026	N	0.28	neutral	N	0.513657157	None	None	N
S/P	0.9402	likely_pathogenic	0.9268	pathogenic	-0.24	Destabilizing	0.996	D	0.659	neutral	None	None	None	None	N
S/Q	0.5627	ambiguous	0.5352	ambiguous	-0.713	Destabilizing	0.988	D	0.595	neutral	None	None	None	None	N
S/R	0.8023	likely_pathogenic	0.7772	pathogenic	-0.473	Destabilizing	0.968	D	0.657	neutral	N	0.505205164	None	None	N
S/T	0.0749	likely_benign	0.0711	benign	-0.523	Destabilizing	0.103	N	0.247	neutral	N	0.430291633	None	None	N
S/V	0.1928	likely_benign	0.1754	benign	-0.24	Destabilizing	0.976	D	0.637	neutral	None	None	None	None	N
S/W	0.5536	ambiguous	0.5401	ambiguous	-0.903	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
S/Y	0.3412	ambiguous	0.3296	benign	-0.647	Destabilizing	0.996	D	0.724	prob.delet.	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.