TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30264	91015;91016;91017	chr2:178552110;178552109;178552108	chr2:179416837;179416836;179416835
N2AB	28623	86092;86093;86094	chr2:178552110;178552109;178552108	chr2:179416837;179416836;179416835
N2A	27696	83311;83312;83313	chr2:178552110;178552109;178552108	chr2:179416837;179416836;179416835
N2B	21199	63820;63821;63822	chr2:178552110;178552109;178552108	chr2:179416837;179416836;179416835
Novex-1	21324	64195;64196;64197	chr2:178552110;178552109;178552108	chr2:179416837;179416836;179416835
Novex-2	21391	64396;64397;64398	chr2:178552110;178552109;178552108	chr2:179416837;179416836;179416835
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-108
• Domain position: 41
• Structural Position: 42
• Q(SASA): 0.1298
• 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
K/R	None	None	0.999	N	0.739	0.214	0.446913017954	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.9654	likely_pathogenic	0.9338	pathogenic	-1.506	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
K/C	0.9265	likely_pathogenic	0.8899	pathogenic	-1.614	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
K/D	0.9967	likely_pathogenic	0.9943	pathogenic	-2.603	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
K/E	0.9293	likely_pathogenic	0.8662	pathogenic	-2.269	Highly Destabilizing	0.999	D	0.733	prob.delet.	N	0.518946827	None	None	N
K/F	0.9795	likely_pathogenic	0.9668	pathogenic	-0.705	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
K/G	0.9793	likely_pathogenic	0.9593	pathogenic	-1.986	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/H	0.8484	likely_pathogenic	0.7801	pathogenic	-1.661	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/I	0.8859	likely_pathogenic	0.8288	pathogenic	-0.114	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
K/L	0.8512	likely_pathogenic	0.7673	pathogenic	-0.114	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/M	0.6237	likely_pathogenic	0.4824	ambiguous	-0.565	Destabilizing	1.0	D	0.783	deleterious	N	0.467343087	None	None	N
K/N	0.9827	likely_pathogenic	0.9654	pathogenic	-2.295	Highly Destabilizing	1.0	D	0.825	deleterious	D	0.525694776	None	None	N
K/P	0.9993	likely_pathogenic	0.9989	pathogenic	-0.563	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/Q	0.5533	ambiguous	0.4215	ambiguous	-1.831	Destabilizing	1.0	D	0.829	deleterious	N	0.494917543	None	None	N
K/R	0.1673	likely_benign	0.1579	benign	-1.148	Destabilizing	0.999	D	0.739	prob.delet.	N	0.467899291	None	None	N
K/S	0.9774	likely_pathogenic	0.9507	pathogenic	-2.673	Highly Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
K/T	0.916	likely_pathogenic	0.8451	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.799	deleterious	N	0.492333422	None	None	N
K/V	0.8593	likely_pathogenic	0.8016	pathogenic	-0.563	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/W	0.9684	likely_pathogenic	0.9524	pathogenic	-0.85	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/Y	0.9183	likely_pathogenic	0.8654	pathogenic	-0.506	Destabilizing	1.0	D	0.847	deleterious	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.