TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19162	57709;57710;57711	chr2:178597598;178597597;178597596	chr2:179462325;179462324;179462323
N2AB	17521	52786;52787;52788	chr2:178597598;178597597;178597596	chr2:179462325;179462324;179462323
N2A	16594	50005;50006;50007	chr2:178597598;178597597;178597596	chr2:179462325;179462324;179462323
N2B	10097	30514;30515;30516	chr2:178597598;178597597;178597596	chr2:179462325;179462324;179462323
Novex-1	10222	30889;30890;30891	chr2:178597598;178597597;178597596	chr2:179462325;179462324;179462323
Novex-2	10289	31090;31091;31092	chr2:178597598;178597597;178597596	chr2:179462325;179462324;179462323
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-117
• Domain position: 68
• Structural Position: 155
• Q(SASA): 0.2179
• 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/C	rs751697133	-0.208	0.97	N	0.562	0.348	0.350964488264	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/C	rs751697133	-0.208	0.97	N	0.562	0.348	0.350964488264	gnomAD-4.0.0	1.59286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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	0.1056	likely_benign	0.1117	benign	-0.838	Destabilizing	0.002	N	0.175	neutral	N	0.462211726	None	None	N
S/C	0.0936	likely_benign	0.0957	benign	-0.814	Destabilizing	0.97	D	0.562	neutral	N	0.476546461	None	None	N
S/D	0.619	likely_pathogenic	0.6528	pathogenic	-1.866	Destabilizing	0.617	D	0.524	neutral	None	None	None	None	N
S/E	0.5986	likely_pathogenic	0.5961	pathogenic	-1.654	Destabilizing	0.617	D	0.521	neutral	None	None	None	None	N
S/F	0.1985	likely_benign	0.2264	benign	-0.746	Destabilizing	0.896	D	0.613	neutral	N	0.505482501	None	None	N
S/G	0.1603	likely_benign	0.1704	benign	-1.223	Destabilizing	0.25	N	0.519	neutral	None	None	None	None	N
S/H	0.3175	likely_benign	0.3216	benign	-1.63	Destabilizing	0.992	D	0.563	neutral	None	None	None	None	N
S/I	0.1705	likely_benign	0.1836	benign	0.142	Stabilizing	0.739	D	0.593	neutral	None	None	None	None	N
S/K	0.7841	likely_pathogenic	0.8083	pathogenic	-0.282	Destabilizing	0.617	D	0.514	neutral	None	None	None	None	N
S/L	0.1256	likely_benign	0.1417	benign	0.142	Stabilizing	0.447	N	0.545	neutral	None	None	None	None	N
S/M	0.1852	likely_benign	0.1946	benign	-0.026	Destabilizing	0.92	D	0.572	neutral	None	None	None	None	N
S/N	0.1937	likely_benign	0.2034	benign	-1.126	Destabilizing	0.617	D	0.536	neutral	None	None	None	None	N
S/P	0.9639	likely_pathogenic	0.9743	pathogenic	-0.151	Destabilizing	0.896	D	0.569	neutral	N	0.458187329	None	None	N
S/Q	0.5086	ambiguous	0.5084	ambiguous	-0.836	Destabilizing	0.92	D	0.545	neutral	None	None	None	None	N
S/R	0.6688	likely_pathogenic	0.6946	pathogenic	-0.728	Destabilizing	0.85	D	0.575	neutral	None	None	None	None	N
S/T	0.068	likely_benign	0.0685	benign	-0.693	Destabilizing	0.001	N	0.173	neutral	N	0.34707528	None	None	N
S/V	0.1693	likely_benign	0.1812	benign	-0.151	Destabilizing	0.447	N	0.545	neutral	None	None	None	None	N
S/W	0.3562	ambiguous	0.3864	ambiguous	-1.094	Destabilizing	0.992	D	0.691	prob.neutral	None	None	None	None	N
S/Y	0.1783	likely_benign	0.2003	benign	-0.603	Destabilizing	0.896	D	0.608	neutral	N	0.486550024	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.