TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16289	49090;49091;49092	chr2:178614649;178614648;178614647	chr2:179479376;179479375;179479374
N2AB	14648	44167;44168;44169	chr2:178614649;178614648;178614647	chr2:179479376;179479375;179479374
N2A	13721	41386;41387;41388	chr2:178614649;178614648;178614647	chr2:179479376;179479375;179479374
N2B	7224	21895;21896;21897	chr2:178614649;178614648;178614647	chr2:179479376;179479375;179479374
Novex-1	7349	22270;22271;22272	chr2:178614649;178614648;178614647	chr2:179479376;179479375;179479374
Novex-2	7416	22471;22472;22473	chr2:178614649;178614648;178614647	chr2:179479376;179479375;179479374
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-110
• Domain position: 28
• Structural Position: 45
• Q(SASA): 0.5521
• Predicted PPI site: I

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/T	None	None	None	N	0.263	0.087	0.101711395817	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.3218	likely_benign	0.2602	benign	-0.006	Destabilizing	0.035	N	0.351	neutral	None	None	None	None	I
K/C	0.6821	likely_pathogenic	0.5931	pathogenic	-0.334	Destabilizing	0.824	D	0.39	neutral	None	None	None	None	I
K/D	0.6234	likely_pathogenic	0.5467	ambiguous	0.005	Stabilizing	0.149	N	0.407	neutral	None	None	None	None	I
K/E	0.198	likely_benign	0.1637	benign	0.041	Stabilizing	0.027	N	0.381	neutral	N	0.443515681	None	None	I
K/F	0.8358	likely_pathogenic	0.7684	pathogenic	-0.053	Destabilizing	0.555	D	0.401	neutral	None	None	None	None	I
K/G	0.5313	ambiguous	0.437	ambiguous	-0.247	Destabilizing	0.149	N	0.395	neutral	None	None	None	None	I
K/H	0.2996	likely_benign	0.2595	benign	-0.457	Destabilizing	0.38	N	0.38	neutral	None	None	None	None	I
K/I	0.3586	ambiguous	0.3109	benign	0.559	Stabilizing	0.188	N	0.424	neutral	N	0.510782303	None	None	I
K/L	0.4009	ambiguous	0.3205	benign	0.559	Stabilizing	0.081	N	0.395	neutral	None	None	None	None	I
K/M	0.2881	likely_benign	0.2338	benign	0.169	Stabilizing	0.555	D	0.378	neutral	None	None	None	None	I
K/N	0.4242	ambiguous	0.3513	ambiguous	-0.006	Destabilizing	0.117	N	0.333	neutral	N	0.499121879	None	None	I
K/P	0.9365	likely_pathogenic	0.8651	pathogenic	0.4	Stabilizing	0.555	D	0.408	neutral	None	None	None	None	I
K/Q	0.1271	likely_benign	0.1095	benign	-0.11	Destabilizing	None	N	0.147	neutral	N	0.482615575	None	None	I
K/R	0.0838	likely_benign	0.0794	benign	-0.182	Destabilizing	None	N	0.137	neutral	N	0.455118483	None	None	I
K/S	0.3881	ambiguous	0.3096	benign	-0.468	Destabilizing	0.035	N	0.326	neutral	None	None	None	None	I
K/T	0.1433	likely_benign	0.121	benign	-0.271	Destabilizing	None	N	0.263	neutral	N	0.443170484	None	None	I
K/V	0.2687	likely_benign	0.2299	benign	0.4	Stabilizing	0.081	N	0.421	neutral	None	None	None	None	I
K/W	0.8472	likely_pathogenic	0.7705	pathogenic	-0.076	Destabilizing	0.935	D	0.431	neutral	None	None	None	None	I
K/Y	0.7236	likely_pathogenic	0.646	pathogenic	0.259	Stabilizing	0.555	D	0.399	neutral	None	None	None	None	I

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.