TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5603	17032;17033;17034	chr2:178732162;178732161;178732160	chr2:179596889;179596888;179596887
N2AB	5286	16081;16082;16083	chr2:178732162;178732161;178732160	chr2:179596889;179596888;179596887
N2A	4359	13300;13301;13302	chr2:178732162;178732161;178732160	chr2:179596889;179596888;179596887
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-39
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.168
• 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
L/R	rs956272919	-1.64	0.995	N	0.85	0.676	0.860091853005	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/R	rs956272919	-1.64	0.995	N	0.85	0.676	0.860091853005	gnomAD-4.0.0	6.81678E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.32406E-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
L/A	0.6256	likely_pathogenic	0.6687	pathogenic	-2.96	Highly Destabilizing	0.851	D	0.73	prob.delet.	None	None	None	None	N
L/C	0.6541	likely_pathogenic	0.6785	pathogenic	-2.471	Highly Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
L/D	0.9416	likely_pathogenic	0.956	pathogenic	-3.55	Highly Destabilizing	0.996	D	0.875	deleterious	None	None	None	None	N
L/E	0.7679	likely_pathogenic	0.8127	pathogenic	-3.286	Highly Destabilizing	0.988	D	0.877	deleterious	None	None	None	None	N
L/F	0.1325	likely_benign	0.1474	benign	-1.778	Destabilizing	0.988	D	0.753	deleterious	None	None	None	None	N
L/G	0.8467	likely_pathogenic	0.8766	pathogenic	-3.56	Highly Destabilizing	0.988	D	0.873	deleterious	None	None	None	None	N
L/H	0.5099	ambiguous	0.5651	pathogenic	-3.045	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
L/I	0.0878	likely_benign	0.0897	benign	-1.189	Destabilizing	0.06	N	0.275	neutral	None	None	None	None	N
L/K	0.6499	likely_pathogenic	0.6973	pathogenic	-2.425	Highly Destabilizing	0.988	D	0.859	deleterious	None	None	None	None	N
L/M	0.1143	likely_benign	0.1209	benign	-1.239	Destabilizing	0.984	D	0.708	prob.delet.	N	0.471896442	None	None	N
L/N	0.7854	likely_pathogenic	0.822	pathogenic	-2.908	Highly Destabilizing	0.996	D	0.865	deleterious	None	None	None	None	N
L/P	0.9297	likely_pathogenic	0.9496	pathogenic	-1.765	Destabilizing	0.995	D	0.873	deleterious	N	0.520552302	None	None	N
L/Q	0.4495	ambiguous	0.5022	ambiguous	-2.705	Highly Destabilizing	0.995	D	0.863	deleterious	N	0.520552302	None	None	N
L/R	0.5395	ambiguous	0.592	pathogenic	-2.158	Highly Destabilizing	0.995	D	0.85	deleterious	N	0.509195997	None	None	N
L/S	0.7297	likely_pathogenic	0.7771	pathogenic	-3.611	Highly Destabilizing	0.988	D	0.839	deleterious	None	None	None	None	N
L/T	0.6144	likely_pathogenic	0.657	pathogenic	-3.187	Highly Destabilizing	0.919	D	0.779	deleterious	None	None	None	None	N
L/V	0.1206	likely_benign	0.1253	benign	-1.765	Destabilizing	0.026	N	0.32	neutral	N	0.448075433	None	None	N
L/W	0.3666	ambiguous	0.4114	ambiguous	-2.225	Highly Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
L/Y	0.4607	ambiguous	0.5006	ambiguous	-1.996	Destabilizing	0.996	D	0.771	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.