TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14166	42721;42722;42723	chr2:178634003;178634002;178634001	chr2:179498730;179498729;179498728
N2AB	12525	37798;37799;37800	chr2:178634003;178634002;178634001	chr2:179498730;179498729;179498728
N2A	11598	35017;35018;35019	chr2:178634003;178634002;178634001	chr2:179498730;179498729;179498728
N2B	5101	15526;15527;15528	chr2:178634003;178634002;178634001	chr2:179498730;179498729;179498728
Novex-1	5226	15901;15902;15903	chr2:178634003;178634002;178634001	chr2:179498730;179498729;179498728
Novex-2	5293	16102;16103;16104	chr2:178634003;178634002;178634001	chr2:179498730;179498729;179498728
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-92
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3997
• 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/A	None	None	0.973	D	0.324	0.392	0.392702134506	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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	0.523	ambiguous	0.4256	ambiguous	-0.527	Destabilizing	0.973	D	0.324	neutral	D	0.589248888	None	None	N
S/C	0.7222	likely_pathogenic	0.6606	pathogenic	-0.306	Destabilizing	1.0	D	0.571	neutral	D	0.686413629	None	None	N
S/D	0.9015	likely_pathogenic	0.8904	pathogenic	-0.738	Destabilizing	0.996	D	0.397	neutral	None	None	None	None	N
S/E	0.9736	likely_pathogenic	0.9636	pathogenic	-0.679	Destabilizing	0.996	D	0.388	neutral	None	None	None	None	N
S/F	0.9556	likely_pathogenic	0.9249	pathogenic	-0.343	Destabilizing	0.999	D	0.645	neutral	D	0.5404641	None	None	N
S/G	0.5027	ambiguous	0.4362	ambiguous	-0.85	Destabilizing	0.996	D	0.325	neutral	None	None	None	None	N
S/H	0.9465	likely_pathogenic	0.9382	pathogenic	-1.358	Destabilizing	1.0	D	0.555	neutral	None	None	None	None	N
S/I	0.9016	likely_pathogenic	0.8321	pathogenic	0.248	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	N
S/K	0.9968	likely_pathogenic	0.995	pathogenic	-0.995	Destabilizing	0.996	D	0.397	neutral	None	None	None	None	N
S/L	0.7417	likely_pathogenic	0.6316	pathogenic	0.248	Stabilizing	0.999	D	0.566	neutral	None	None	None	None	N
S/M	0.8395	likely_pathogenic	0.7821	pathogenic	0.391	Stabilizing	1.0	D	0.557	neutral	None	None	None	None	N
S/N	0.5798	likely_pathogenic	0.568	pathogenic	-1.042	Destabilizing	0.999	D	0.436	neutral	None	None	None	None	N
S/P	0.9704	likely_pathogenic	0.9495	pathogenic	0.025	Stabilizing	0.217	N	0.241	neutral	D	0.622508215	None	None	N
S/Q	0.9707	likely_pathogenic	0.9646	pathogenic	-0.982	Destabilizing	1.0	D	0.505	neutral	None	None	None	None	N
S/R	0.9945	likely_pathogenic	0.9909	pathogenic	-1.038	Destabilizing	1.0	D	0.578	neutral	None	None	None	None	N
S/T	0.2063	likely_benign	0.1945	benign	-0.879	Destabilizing	0.994	D	0.351	neutral	N	0.504217862	None	None	N
S/V	0.8999	likely_pathogenic	0.8423	pathogenic	0.025	Stabilizing	0.999	D	0.591	neutral	None	None	None	None	N
S/W	0.96	likely_pathogenic	0.9421	pathogenic	-0.528	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
S/Y	0.9085	likely_pathogenic	0.8712	pathogenic	-0.243	Destabilizing	0.999	D	0.643	neutral	D	0.684672034	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.