TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5594	17005;17006;17007	chr2:178732189;178732188;178732187	chr2:179596916;179596915;179596914
N2AB	5277	16054;16055;16056	chr2:178732189;178732188;178732187	chr2:179596916;179596915;179596914
N2A	4350	13273;13274;13275	chr2:178732189;178732188;178732187	chr2:179596916;179596915;179596914
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-39
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.2688
• 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
F/S	rs1210237703	-1.801	0.065	N	0.516	0.241	0.73377832567	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
F/S	rs1210237703	-1.801	0.065	N	0.516	0.241	0.73377832567	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	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
F/A	0.6604	likely_pathogenic	0.7763	pathogenic	-1.863	Destabilizing	0.031	N	0.466	neutral	None	None	None	None	N
F/C	0.5574	ambiguous	0.701	pathogenic	-1.102	Destabilizing	0.993	D	0.667	neutral	N	0.50587418	None	None	N
F/D	0.8787	likely_pathogenic	0.9286	pathogenic	0.041	Stabilizing	0.704	D	0.689	prob.neutral	None	None	None	None	N
F/E	0.9013	likely_pathogenic	0.9427	pathogenic	0.12	Stabilizing	0.543	D	0.639	neutral	None	None	None	None	N
F/G	0.8646	likely_pathogenic	0.9232	pathogenic	-2.179	Highly Destabilizing	0.704	D	0.641	neutral	None	None	None	None	N
F/H	0.7106	likely_pathogenic	0.8057	pathogenic	-0.561	Destabilizing	0.944	D	0.633	neutral	None	None	None	None	N
F/I	0.3148	likely_benign	0.4011	ambiguous	-0.94	Destabilizing	0.473	N	0.503	neutral	D	0.52870973	None	None	N
F/K	0.9113	likely_pathogenic	0.9542	pathogenic	-0.904	Destabilizing	0.543	D	0.671	neutral	None	None	None	None	N
F/L	0.8488	likely_pathogenic	0.9058	pathogenic	-0.94	Destabilizing	0.006	N	0.265	neutral	D	0.530960601	None	None	N
F/M	0.5624	ambiguous	0.6683	pathogenic	-0.778	Destabilizing	0.893	D	0.628	neutral	None	None	None	None	N
F/N	0.761	likely_pathogenic	0.8444	pathogenic	-0.907	Destabilizing	0.893	D	0.693	prob.neutral	None	None	None	None	N
F/P	0.9844	likely_pathogenic	0.9921	pathogenic	-1.237	Destabilizing	0.944	D	0.688	prob.neutral	None	None	None	None	N
F/Q	0.8646	likely_pathogenic	0.923	pathogenic	-0.928	Destabilizing	0.176	N	0.534	neutral	None	None	None	None	N
F/R	0.813	likely_pathogenic	0.8917	pathogenic	-0.369	Destabilizing	0.893	D	0.69	prob.neutral	None	None	None	None	N
F/S	0.5235	ambiguous	0.6545	pathogenic	-1.801	Destabilizing	0.065	N	0.516	neutral	N	0.516164507	None	None	N
F/T	0.5515	ambiguous	0.6677	pathogenic	-1.628	Destabilizing	0.704	D	0.642	neutral	None	None	None	None	N
F/V	0.2919	likely_benign	0.378	ambiguous	-1.237	Destabilizing	0.023	N	0.369	neutral	N	0.520780893	None	None	N
F/W	0.5686	likely_pathogenic	0.6669	pathogenic	-0.187	Destabilizing	0.995	D	0.625	neutral	None	None	None	None	N
F/Y	0.2606	likely_benign	0.3262	benign	-0.358	Destabilizing	0.784	D	0.569	neutral	N	0.521821043	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.