TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27987	84184;84185;84186	chr2:178562173;178562172;178562171	chr2:179426900;179426899;179426898
N2AB	26346	79261;79262;79263	chr2:178562173;178562172;178562171	chr2:179426900;179426899;179426898
N2A	25419	76480;76481;76482	chr2:178562173;178562172;178562171	chr2:179426900;179426899;179426898
N2B	18922	56989;56990;56991	chr2:178562173;178562172;178562171	chr2:179426900;179426899;179426898
Novex-1	19047	57364;57365;57366	chr2:178562173;178562172;178562171	chr2:179426900;179426899;179426898
Novex-2	19114	57565;57566;57567	chr2:178562173;178562172;178562171	chr2:179426900;179426899;179426898
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-142
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.6414
• 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/R	None	None	0.001	N	0.136	0.091	0.329282125956	gnomAD-4.0.0	1.5929E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02718E-05

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	0.3643	ambiguous	0.3563	ambiguous	-0.276	Destabilizing	0.116	N	0.361	neutral	None	None	None	None	I
K/C	0.6211	likely_pathogenic	0.5958	pathogenic	-0.374	Destabilizing	0.944	D	0.417	neutral	None	None	None	None	I
K/D	0.7174	likely_pathogenic	0.7111	pathogenic	0.369	Stabilizing	0.388	N	0.358	neutral	None	None	None	None	I
K/E	0.2471	likely_benign	0.2562	benign	0.427	Stabilizing	0.193	N	0.375	neutral	N	0.451363667	None	None	I
K/F	0.6838	likely_pathogenic	0.701	pathogenic	-0.229	Destabilizing	0.818	D	0.394	neutral	None	None	None	None	I
K/G	0.5698	likely_pathogenic	0.5853	pathogenic	-0.556	Destabilizing	0.241	N	0.387	neutral	None	None	None	None	I
K/H	0.2471	likely_benign	0.2424	benign	-0.849	Destabilizing	0.818	D	0.365	neutral	None	None	None	None	I
K/I	0.2539	likely_benign	0.2582	benign	0.407	Stabilizing	0.627	D	0.402	neutral	N	0.445267201	None	None	I
K/L	0.3322	likely_benign	0.3491	ambiguous	0.407	Stabilizing	0.388	N	0.374	neutral	None	None	None	None	I
K/M	0.2323	likely_benign	0.2469	benign	0.186	Stabilizing	0.981	D	0.358	neutral	None	None	None	None	I
K/N	0.5066	ambiguous	0.5185	ambiguous	0.057	Stabilizing	0.193	N	0.361	neutral	N	0.520591679	None	None	I
K/P	0.8946	likely_pathogenic	0.9084	pathogenic	0.21	Stabilizing	0.818	D	0.363	neutral	None	None	None	None	I
K/Q	0.1377	likely_benign	0.1377	benign	-0.064	Destabilizing	0.324	N	0.387	neutral	N	0.461620733	None	None	I
K/R	0.0654	likely_benign	0.0681	benign	-0.201	Destabilizing	0.001	N	0.136	neutral	N	0.447075355	None	None	I
K/S	0.39	ambiguous	0.381	ambiguous	-0.59	Destabilizing	0.002	N	0.206	neutral	None	None	None	None	I
K/T	0.145	likely_benign	0.1464	benign	-0.346	Destabilizing	0.193	N	0.338	neutral	N	0.477011473	None	None	I
K/V	0.2694	likely_benign	0.2611	benign	0.21	Stabilizing	0.69	D	0.365	neutral	None	None	None	None	I
K/W	0.6681	likely_pathogenic	0.6775	pathogenic	-0.136	Destabilizing	0.981	D	0.515	neutral	None	None	None	None	I
K/Y	0.5423	ambiguous	0.5507	ambiguous	0.18	Stabilizing	0.818	D	0.388	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.