TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18737	56434;56435;56436	chr2:178599692;178599691;178599690	chr2:179464419;179464418;179464417
N2AB	17096	51511;51512;51513	chr2:178599692;178599691;178599690	chr2:179464419;179464418;179464417
N2A	16169	48730;48731;48732	chr2:178599692;178599691;178599690	chr2:179464419;179464418;179464417
N2B	9672	29239;29240;29241	chr2:178599692;178599691;178599690	chr2:179464419;179464418;179464417
Novex-1	9797	29614;29615;29616	chr2:178599692;178599691;178599690	chr2:179464419;179464418;179464417
Novex-2	9864	29815;29816;29817	chr2:178599692;178599691;178599690	chr2:179464419;179464418;179464417
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-116
• Domain position: 50
• Structural Position: 115
• Q(SASA): 0.8408
• 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
H/Y	None	None	0.999	N	0.581	0.431	0.278968121808	gnomAD-4.0.0	1.59293E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43456E-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
H/A	0.5393	ambiguous	0.5601	ambiguous	-0.415	Destabilizing	0.999	D	0.55	neutral	None	None	None	None	N
H/C	0.3205	likely_benign	0.3402	ambiguous	0.337	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
H/D	0.4589	ambiguous	0.4899	ambiguous	-0.205	Destabilizing	1.0	D	0.652	neutral	N	0.501402046	None	None	N
H/E	0.5473	ambiguous	0.553	ambiguous	-0.141	Destabilizing	0.999	D	0.574	neutral	None	None	None	None	N
H/F	0.5088	ambiguous	0.5141	ambiguous	0.412	Stabilizing	1.0	D	0.642	neutral	None	None	None	None	N
H/G	0.5837	likely_pathogenic	0.5997	pathogenic	-0.752	Destabilizing	0.999	D	0.566	neutral	None	None	None	None	N
H/I	0.5736	likely_pathogenic	0.6127	pathogenic	0.487	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
H/K	0.4076	ambiguous	0.4378	ambiguous	-0.368	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
H/L	0.2964	likely_benign	0.2978	benign	0.487	Stabilizing	1.0	D	0.651	neutral	N	0.472769184	None	None	N
H/M	0.6849	likely_pathogenic	0.6929	pathogenic	0.381	Stabilizing	1.0	D	0.584	neutral	None	None	None	None	N
H/N	0.2036	likely_benign	0.227	benign	-0.267	Destabilizing	0.999	D	0.582	neutral	N	0.492166487	None	None	N
H/P	0.5545	ambiguous	0.6112	pathogenic	0.21	Stabilizing	1.0	D	0.597	neutral	N	0.464059452	None	None	N
H/Q	0.3501	ambiguous	0.3629	ambiguous	-0.079	Destabilizing	1.0	D	0.681	prob.neutral	N	0.452285073	None	None	N
H/R	0.1457	likely_benign	0.1584	benign	-0.912	Destabilizing	1.0	D	0.679	prob.neutral	N	0.424397126	None	None	N
H/S	0.4465	ambiguous	0.4547	ambiguous	-0.273	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
H/T	0.484	ambiguous	0.5067	ambiguous	-0.112	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
H/V	0.4936	ambiguous	0.5241	ambiguous	0.21	Stabilizing	1.0	D	0.656	neutral	None	None	None	None	N
H/W	0.5475	ambiguous	0.5561	ambiguous	0.539	Stabilizing	1.0	D	0.636	neutral	None	None	None	None	N
H/Y	0.1854	likely_benign	0.2	benign	0.786	Stabilizing	0.999	D	0.581	neutral	N	0.493206637	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.