TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4718	14377;14378;14379	chr2:178738301;178738300;178738299	chr2:179603028;179603027;179603026
N2AB	4401	13426;13427;13428	chr2:178738301;178738300;178738299	chr2:179603028;179603027;179603026
N2A	3474	10645;10646;10647	chr2:178738301;178738300;178738299	chr2:179603028;179603027;179603026
N2B	4355	13288;13289;13290	chr2:178738301;178738300;178738299	chr2:179603028;179603027;179603026
Novex-1	4480	13663;13664;13665	chr2:178738301;178738300;178738299	chr2:179603028;179603027;179603026
Novex-2	4547	13864;13865;13866	chr2:178738301;178738300;178738299	chr2:179603028;179603027;179603026
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-30
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.6905
• 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/E	rs757119133	0.42	0.946	N	0.617	0.251	0.191931220699	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.69E-05	0
K/E	rs757119133	0.42	0.946	N	0.617	0.251	0.191931220699	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
K/E	rs757119133	0.42	0.946	N	0.617	0.251	0.191931220699	gnomAD-4.0.0	5.14421E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.95084E-05	0	1.6019E-05
K/I	rs753558755	0.745	0.811	N	0.578	0.219	0.300110245524	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	0	0	None	0	3.92773E-04	None	0	None	0	0	0
K/I	rs753558755	0.745	0.811	N	0.578	0.219	0.300110245524	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92456E-04	None	0	0	0	0	0
K/I	rs753558755	0.745	0.811	N	0.578	0.219	0.300110245524	gnomAD-4.0.0	5.57814E-06	None	None	None	None	N	None	0	0	None	0	2.00974E-04	None	0	0	0	0	0
K/R	rs753558755	None	0.982	N	0.615	0.174	0.231231049324	gnomAD-4.0.0	1.36869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73551E-04	8.99539E-07	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	0.5398	ambiguous	0.6696	pathogenic	-0.55	Destabilizing	0.851	D	0.597	neutral	None	None	None	None	N
K/C	0.821	likely_pathogenic	0.8602	pathogenic	-0.631	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
K/D	0.859	likely_pathogenic	0.9202	pathogenic	0.216	Stabilizing	0.996	D	0.663	neutral	None	None	None	None	N
K/E	0.3408	ambiguous	0.4634	ambiguous	0.314	Stabilizing	0.946	D	0.617	neutral	N	0.349013657	None	None	N
K/F	0.8931	likely_pathogenic	0.9319	pathogenic	-0.372	Destabilizing	0.976	D	0.683	prob.neutral	None	None	None	None	N
K/G	0.7353	likely_pathogenic	0.8371	pathogenic	-0.873	Destabilizing	0.988	D	0.608	neutral	None	None	None	None	N
K/H	0.3992	ambiguous	0.487	ambiguous	-1.063	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
K/I	0.4754	ambiguous	0.5269	ambiguous	0.268	Stabilizing	0.811	D	0.578	neutral	N	0.444378342	None	None	N
K/L	0.5463	ambiguous	0.6307	pathogenic	0.268	Stabilizing	0.034	N	0.484	neutral	None	None	None	None	N
K/M	0.3885	ambiguous	0.4644	ambiguous	0.047	Stabilizing	0.976	D	0.665	neutral	None	None	None	None	N
K/N	0.6324	likely_pathogenic	0.7654	pathogenic	-0.3	Destabilizing	0.995	D	0.643	neutral	N	0.447413739	None	None	N
K/P	0.9649	likely_pathogenic	0.9812	pathogenic	0.025	Stabilizing	0.996	D	0.663	neutral	None	None	None	None	N
K/Q	0.1855	likely_benign	0.2547	benign	-0.358	Destabilizing	0.995	D	0.677	prob.neutral	N	0.447413739	None	None	N
K/R	0.0871	likely_benign	0.0985	benign	-0.353	Destabilizing	0.982	D	0.615	neutral	N	0.443872049	None	None	N
K/S	0.5466	ambiguous	0.6981	pathogenic	-1.001	Destabilizing	0.959	D	0.594	neutral	None	None	None	None	N
K/T	0.2083	likely_benign	0.2878	benign	-0.696	Destabilizing	0.896	D	0.584	neutral	N	0.438186984	None	None	N
K/V	0.3743	ambiguous	0.4317	ambiguous	0.025	Stabilizing	0.034	N	0.487	neutral	None	None	None	None	N
K/W	0.887	likely_pathogenic	0.9255	pathogenic	-0.243	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
K/Y	0.79	likely_pathogenic	0.8477	pathogenic	0.05	Stabilizing	0.996	D	0.672	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.