TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25904	77935;77936;77937	chr2:178568422;178568421;178568420	chr2:179433149;179433148;179433147
N2AB	24263	73012;73013;73014	chr2:178568422;178568421;178568420	chr2:179433149;179433148;179433147
N2A	23336	70231;70232;70233	chr2:178568422;178568421;178568420	chr2:179433149;179433148;179433147
N2B	16839	50740;50741;50742	chr2:178568422;178568421;178568420	chr2:179433149;179433148;179433147
Novex-1	16964	51115;51116;51117	chr2:178568422;178568421;178568420	chr2:179433149;179433148;179433147
Novex-2	17031	51316;51317;51318	chr2:178568422;178568421;178568420	chr2:179433149;179433148;179433147
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-76
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.2232
• 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/R	None	None	0.967	D	0.659	0.385	0.268211541103	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.1626	likely_benign	0.182	benign	-0.869	Destabilizing	0.693	D	0.407	neutral	None	None	None	None	N
S/C	0.1966	likely_benign	0.2171	benign	-0.653	Destabilizing	0.999	D	0.617	neutral	D	0.526863773	None	None	N
S/D	0.7654	likely_pathogenic	0.779	pathogenic	-0.611	Destabilizing	0.916	D	0.561	neutral	None	None	None	None	N
S/E	0.9246	likely_pathogenic	0.9328	pathogenic	-0.561	Destabilizing	0.916	D	0.562	neutral	None	None	None	None	N
S/F	0.5486	ambiguous	0.6231	pathogenic	-0.933	Destabilizing	0.987	D	0.685	prob.neutral	None	None	None	None	N
S/G	0.1608	likely_benign	0.1764	benign	-1.158	Destabilizing	0.892	D	0.45	neutral	N	0.516094644	None	None	N
S/H	0.7609	likely_pathogenic	0.7701	pathogenic	-1.55	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
S/I	0.6151	likely_pathogenic	0.6775	pathogenic	-0.19	Destabilizing	0.967	D	0.699	prob.neutral	N	0.497238628	None	None	N
S/K	0.953	likely_pathogenic	0.9554	pathogenic	-0.667	Destabilizing	0.916	D	0.563	neutral	None	None	None	None	N
S/L	0.1846	likely_benign	0.2047	benign	-0.19	Destabilizing	0.845	D	0.593	neutral	None	None	None	None	N
S/M	0.3682	ambiguous	0.3791	ambiguous	0.034	Stabilizing	0.999	D	0.614	neutral	None	None	None	None	N
S/N	0.3309	likely_benign	0.3656	ambiguous	-0.834	Destabilizing	0.892	D	0.57	neutral	N	0.52128982	None	None	N
S/P	0.969	likely_pathogenic	0.9741	pathogenic	-0.382	Destabilizing	0.987	D	0.655	neutral	None	None	None	None	N
S/Q	0.8821	likely_pathogenic	0.8822	pathogenic	-0.92	Destabilizing	0.987	D	0.643	neutral	None	None	None	None	N
S/R	0.9378	likely_pathogenic	0.9425	pathogenic	-0.634	Destabilizing	0.967	D	0.659	neutral	D	0.523311405	None	None	N
S/T	0.0883	likely_benign	0.0865	benign	-0.781	Destabilizing	0.025	N	0.333	neutral	N	0.427550153	None	None	N
S/V	0.5176	ambiguous	0.5673	pathogenic	-0.382	Destabilizing	0.95	D	0.633	neutral	None	None	None	None	N
S/W	0.8029	likely_pathogenic	0.8283	pathogenic	-0.932	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
S/Y	0.5379	ambiguous	0.588	pathogenic	-0.637	Destabilizing	0.996	D	0.689	prob.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.