TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8632	26119;26120;26121	chr2:178715520;178715519;178715518	chr2:179580247;179580246;179580245
N2AB	8315	25168;25169;25170	chr2:178715520;178715519;178715518	chr2:179580247;179580246;179580245
N2A	7388	22387;22388;22389	chr2:178715520;178715519;178715518	chr2:179580247;179580246;179580245
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-71
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.447
• 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/G	None	None	0.997	D	0.434	0.368	0.388812400583	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.134	likely_benign	0.1372	benign	-0.645	Destabilizing	0.559	D	0.417	neutral	None	None	None	None	N
S/C	0.2301	likely_benign	0.2092	benign	-0.386	Destabilizing	1.0	D	0.666	neutral	N	0.509903559	None	None	N
S/D	0.5295	ambiguous	0.5197	ambiguous	0.22	Stabilizing	0.999	D	0.517	neutral	None	None	None	None	N
S/E	0.6955	likely_pathogenic	0.6972	pathogenic	0.145	Stabilizing	0.997	D	0.484	neutral	None	None	None	None	N
S/F	0.2733	likely_benign	0.2785	benign	-1.13	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
S/G	0.1364	likely_benign	0.1335	benign	-0.789	Destabilizing	0.997	D	0.434	neutral	D	0.534489047	None	None	N
S/H	0.3735	ambiguous	0.3429	ambiguous	-1.247	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
S/I	0.2005	likely_benign	0.2069	benign	-0.388	Destabilizing	0.983	D	0.607	neutral	N	0.503471551	None	None	N
S/K	0.7006	likely_pathogenic	0.6966	pathogenic	-0.535	Destabilizing	0.999	D	0.496	neutral	None	None	None	None	N
S/L	0.1784	likely_benign	0.1942	benign	-0.388	Destabilizing	0.987	D	0.545	neutral	None	None	None	None	N
S/M	0.304	likely_benign	0.3168	benign	-0.082	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
S/N	0.1401	likely_benign	0.1399	benign	-0.265	Destabilizing	0.988	D	0.552	neutral	N	0.490861025	None	None	N
S/P	0.8564	likely_pathogenic	0.8858	pathogenic	-0.444	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
S/Q	0.5694	likely_pathogenic	0.5467	ambiguous	-0.518	Destabilizing	1.0	D	0.576	neutral	None	None	None	None	N
S/R	0.5837	likely_pathogenic	0.5743	pathogenic	-0.325	Destabilizing	1.0	D	0.701	prob.neutral	D	0.522823908	None	None	N
S/T	0.1056	likely_benign	0.1073	benign	-0.413	Destabilizing	0.786	D	0.438	neutral	D	0.523301123	None	None	N
S/V	0.24	likely_benign	0.2404	benign	-0.444	Destabilizing	0.438	N	0.526	neutral	None	None	None	None	N
S/W	0.5185	ambiguous	0.5026	ambiguous	-1.066	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
S/Y	0.2708	likely_benign	0.2654	benign	-0.817	Destabilizing	1.0	D	0.715	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.