TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9994	30205;30206;30207	chr2:178704390;178704389;178704388	chr2:179569117;179569116;179569115
N2AB	9677	29254;29255;29256	chr2:178704390;178704389;178704388	chr2:179569117;179569116;179569115
N2A	8750	26473;26474;26475	chr2:178704390;178704389;178704388	chr2:179569117;179569116;179569115
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-85
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4881
• 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/R	None	None	0.966	None	0.405	0.24	0.282179105231	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86067E-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
H/A	0.4071	ambiguous	0.5664	pathogenic	0.18	Stabilizing	0.525	D	0.429	neutral	None	None	None	None	N
H/C	0.3942	ambiguous	0.4555	ambiguous	0.968	Stabilizing	0.998	D	0.563	neutral	None	None	None	None	N
H/D	0.3317	likely_benign	0.4494	ambiguous	0.121	Stabilizing	0.801	D	0.418	neutral	None	None	None	None	N
H/E	0.3956	ambiguous	0.5158	ambiguous	0.182	Stabilizing	0.842	D	0.347	neutral	None	None	None	None	N
H/F	0.468	ambiguous	0.5521	ambiguous	1.071	Stabilizing	0.991	D	0.501	neutral	None	None	None	None	N
H/G	0.4784	ambiguous	0.6142	pathogenic	-0.159	Destabilizing	0.842	D	0.462	neutral	None	None	None	None	N
H/I	0.4938	ambiguous	0.6309	pathogenic	1.076	Stabilizing	0.974	D	0.567	neutral	None	None	None	None	N
H/K	0.2849	likely_benign	0.3636	ambiguous	0.412	Stabilizing	0.842	D	0.404	neutral	None	None	None	None	N
H/L	0.1898	likely_benign	0.2422	benign	1.076	Stabilizing	0.801	D	0.5	neutral	None	None	None	None	N
H/M	0.6341	likely_pathogenic	0.7416	pathogenic	0.849	Stabilizing	0.998	D	0.535	neutral	None	None	None	None	N
H/N	0.1369	likely_benign	0.1889	benign	0.46	Stabilizing	0.801	D	0.368	neutral	None	None	None	None	N
H/P	0.1241	likely_benign	0.1663	benign	0.803	Stabilizing	0.005	N	0.253	neutral	None	None	None	None	N
H/Q	0.2412	likely_benign	0.3439	ambiguous	0.622	Stabilizing	0.966	D	0.425	neutral	None	None	None	None	N
H/R	0.1269	likely_benign	0.1615	benign	-0.296	Destabilizing	0.966	D	0.405	neutral	None	None	None	None	N
H/S	0.3368	likely_benign	0.4783	ambiguous	0.541	Stabilizing	0.172	N	0.285	neutral	None	None	None	None	N
H/T	0.4062	ambiguous	0.5709	pathogenic	0.704	Stabilizing	0.728	D	0.481	neutral	None	None	None	None	N
H/V	0.433	ambiguous	0.5642	pathogenic	0.803	Stabilizing	0.974	D	0.516	neutral	None	None	None	None	N
H/W	0.5922	likely_pathogenic	0.6485	pathogenic	1.163	Stabilizing	0.998	D	0.609	neutral	None	None	None	None	N
H/Y	0.1603	likely_benign	0.1899	benign	1.401	Stabilizing	0.989	D	0.435	neutral	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.