TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18602	56029;56030;56031	chr2:178601100;178601099;178601098	chr2:179465827;179465826;179465825
N2AB	16961	51106;51107;51108	chr2:178601100;178601099;178601098	chr2:179465827;179465826;179465825
N2A	16034	48325;48326;48327	chr2:178601100;178601099;178601098	chr2:179465827;179465826;179465825
N2B	9537	28834;28835;28836	chr2:178601100;178601099;178601098	chr2:179465827;179465826;179465825
Novex-1	9662	29209;29210;29211	chr2:178601100;178601099;178601098	chr2:179465827;179465826;179465825
Novex-2	9729	29410;29411;29412	chr2:178601100;178601099;178601098	chr2:179465827;179465826;179465825
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-23
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.3907
• 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
P/H	rs559554374	-1.7	1.0	N	0.87	0.47	0.567170738818	gnomAD-2.1.1	8.41E-06	None	None	None	None	N	None	0	0	None	0	1.13572E-04	None	0	None	0	0	0
P/H	rs559554374	-1.7	1.0	N	0.87	0.47	0.567170738818	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.9478E-04	None	0	0	0	0	0
P/H	rs559554374	-1.7	1.0	N	0.87	0.47	0.567170738818	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
P/H	rs559554374	-1.7	1.0	N	0.87	0.47	0.567170738818	gnomAD-4.0.0	2.60146E-06	None	None	None	None	N	None	0	0	None	0	4.88806E-05	None	0	0	0	0	0
P/S	rs781300931	None	0.999	N	0.771	0.377	0.303781844768	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
P/S	rs781300931	None	0.999	N	0.771	0.377	0.303781844768	gnomAD-4.0.0	5.61931E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.66836E-06	0	0
P/T	rs781300931	-2.081	0.999	N	0.777	0.39	0.454893017966	gnomAD-2.1.1	8.42E-06	None	None	None	None	N	None	0	0	None	0	5.68E-05	None	0	None	0	9.29E-06	0
P/T	rs781300931	-2.081	0.999	N	0.777	0.39	0.454893017966	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/T	rs781300931	-2.081	0.999	N	0.777	0.39	0.454893017966	gnomAD-4.0.0	1.8731E-06	None	None	None	None	N	None	2.6881E-05	0	None	0	0	None	0	0	8.5204E-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
P/A	0.1037	likely_benign	0.1024	benign	-1.932	Destabilizing	0.996	D	0.609	neutral	N	0.472712014	None	None	N
P/C	0.7471	likely_pathogenic	0.6843	pathogenic	-1.274	Destabilizing	0.844	D	0.501	neutral	None	None	None	None	N
P/D	0.8443	likely_pathogenic	0.8085	pathogenic	-2.687	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/E	0.501	ambiguous	0.466	ambiguous	-2.506	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
P/F	0.7936	likely_pathogenic	0.6982	pathogenic	-1.322	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/G	0.582	likely_pathogenic	0.5556	ambiguous	-2.385	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
P/H	0.4661	ambiguous	0.3851	ambiguous	-2.014	Highly Destabilizing	1.0	D	0.87	deleterious	N	0.489355498	None	None	N
P/I	0.4796	ambiguous	0.4019	ambiguous	-0.687	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/K	0.4015	ambiguous	0.3705	ambiguous	-1.781	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/L	0.2409	likely_benign	0.1896	benign	-0.687	Destabilizing	0.999	D	0.812	deleterious	N	0.495431884	None	None	N
P/M	0.4494	ambiguous	0.4017	ambiguous	-0.534	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/N	0.7269	likely_pathogenic	0.6486	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/Q	0.2825	likely_benign	0.2387	benign	-1.977	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/R	0.3232	likely_benign	0.2848	benign	-1.457	Destabilizing	1.0	D	0.89	deleterious	N	0.518332447	None	None	N
P/S	0.3078	likely_benign	0.2681	benign	-2.526	Highly Destabilizing	0.999	D	0.771	deleterious	N	0.480770669	None	None	N
P/T	0.2666	likely_benign	0.2275	benign	-2.217	Highly Destabilizing	0.999	D	0.777	deleterious	N	0.484809594	None	None	N
P/V	0.3318	likely_benign	0.2791	benign	-1.076	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
P/W	0.9142	likely_pathogenic	0.8661	pathogenic	-1.785	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/Y	0.7299	likely_pathogenic	0.6487	pathogenic	-1.377	Destabilizing	1.0	D	0.885	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.