TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8595	26008;26009;26010	chr2:178715631;178715630;178715629	chr2:179580358;179580357;179580356
N2AB	8278	25057;25058;25059	chr2:178715631;178715630;178715629	chr2:179580358;179580357;179580356
N2A	7351	22276;22277;22278	chr2:178715631;178715630;178715629	chr2:179580358;179580357;179580356
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-71
• Domain position: 47
• Structural Position: 115
• Q(SASA): 0.3954
• 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/N	None	None	0.019	N	0.073	0.06	0.0806252709748	gnomAD-4.0.0	1.59172E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85914E-06	0	0
K/Q	None	None	0.006	N	0.189	0.184	0.104622674875	gnomAD-4.0.0	1.36859E-06	None	None	None	None	N	None	0	4.47507E-05	None	0	0	None	0	0	0	0	0
K/R	rs774140425	-0.301	0.241	N	0.285	0.09	0.119812018005	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	1.16117E-04	None	0	0	None	0	None	0	8.88E-06	0
K/R	rs774140425	-0.301	0.241	N	0.285	0.09	0.119812018005	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
K/R	rs774140425	-0.301	0.241	N	0.285	0.09	0.119812018005	gnomAD-4.0.0	1.66584E-05	None	None	None	None	N	None	0	1.01764E-04	None	0	0	None	0	0	7.18119E-06	0	1.13824E-04

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	0.5288	ambiguous	0.4684	ambiguous	-0.73	Destabilizing	0.485	N	0.299	neutral	None	None	None	None	N
K/C	0.8068	likely_pathogenic	0.7734	pathogenic	-0.613	Destabilizing	0.997	D	0.453	neutral	None	None	None	None	N
K/D	0.6561	likely_pathogenic	0.6116	pathogenic	-0.041	Destabilizing	0.014	N	0.163	neutral	None	None	None	None	N
K/E	0.342	ambiguous	0.3063	benign	0.082	Stabilizing	0.003	N	0.08	neutral	N	0.456554715	None	None	N
K/F	0.893	likely_pathogenic	0.8522	pathogenic	-0.423	Destabilizing	0.975	D	0.425	neutral	None	None	None	None	N
K/G	0.64	likely_pathogenic	0.5793	pathogenic	-1.104	Destabilizing	0.653	D	0.325	neutral	None	None	None	None	N
K/H	0.3544	ambiguous	0.3083	benign	-1.421	Destabilizing	0.931	D	0.376	neutral	None	None	None	None	N
K/I	0.5286	ambiguous	0.4776	ambiguous	0.244	Stabilizing	0.418	N	0.448	neutral	N	0.459201288	None	None	N
K/L	0.5149	ambiguous	0.4622	ambiguous	0.244	Stabilizing	0.118	N	0.399	neutral	None	None	None	None	N
K/M	0.4077	ambiguous	0.3578	ambiguous	0.162	Stabilizing	0.795	D	0.375	neutral	None	None	None	None	N
K/N	0.496	ambiguous	0.4476	ambiguous	-0.482	Destabilizing	0.019	N	0.073	neutral	N	0.477450538	None	None	N
K/P	0.8563	likely_pathogenic	0.8323	pathogenic	-0.051	Destabilizing	0.97	D	0.437	neutral	None	None	None	None	N
K/Q	0.2158	likely_benign	0.1889	benign	-0.518	Destabilizing	0.006	N	0.189	neutral	N	0.477963879	None	None	N
K/R	0.0849	likely_benign	0.0814	benign	-0.6	Destabilizing	0.241	N	0.285	neutral	N	0.455202822	None	None	N
K/S	0.5512	ambiguous	0.4919	ambiguous	-1.187	Destabilizing	0.485	N	0.239	neutral	None	None	None	None	N
K/T	0.2733	likely_benign	0.2344	benign	-0.844	Destabilizing	0.508	D	0.331	neutral	N	0.470050614	None	None	N
K/V	0.4927	ambiguous	0.4441	ambiguous	-0.051	Destabilizing	0.15	N	0.423	neutral	None	None	None	None	N
K/W	0.8563	likely_pathogenic	0.8185	pathogenic	-0.28	Destabilizing	0.998	D	0.531	neutral	None	None	None	None	N
K/Y	0.7095	likely_pathogenic	0.6455	pathogenic	0.002	Stabilizing	0.601	D	0.397	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.