TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30518	91777;91778;91779	chr2:178550979;178550978;178550977	chr2:179415706;179415705;179415704
N2AB	28877	86854;86855;86856	chr2:178550979;178550978;178550977	chr2:179415706;179415705;179415704
N2A	27950	84073;84074;84075	chr2:178550979;178550978;178550977	chr2:179415706;179415705;179415704
N2B	21453	64582;64583;64584	chr2:178550979;178550978;178550977	chr2:179415706;179415705;179415704
Novex-1	21578	64957;64958;64959	chr2:178550979;178550978;178550977	chr2:179415706;179415705;179415704
Novex-2	21645	65158;65159;65160	chr2:178550979;178550978;178550977	chr2:179415706;179415705;179415704
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-110
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.471
• 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
R/G	None	None	0.958	N	0.593	0.336	0.586816528483	gnomAD-4.0.0	3.18731E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72122E-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
R/A	0.6172	likely_pathogenic	0.6602	pathogenic	-0.263	Destabilizing	0.862	D	0.563	neutral	None	None	None	None	N
R/C	0.3054	likely_benign	0.3566	ambiguous	-0.21	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
R/D	0.8776	likely_pathogenic	0.8936	pathogenic	0.014	Stabilizing	0.991	D	0.639	neutral	None	None	None	None	N
R/E	0.5746	likely_pathogenic	0.6021	pathogenic	0.107	Stabilizing	0.938	D	0.477	neutral	None	None	None	None	N
R/F	0.7681	likely_pathogenic	0.8064	pathogenic	-0.301	Destabilizing	0.997	D	0.797	deleterious	None	None	None	None	N
R/G	0.499	ambiguous	0.5773	pathogenic	-0.525	Destabilizing	0.958	D	0.593	neutral	N	0.490225913	None	None	N
R/H	0.1666	likely_benign	0.184	benign	-1.013	Destabilizing	0.997	D	0.433	neutral	None	None	None	None	N
R/I	0.4585	ambiguous	0.5126	ambiguous	0.416	Stabilizing	0.996	D	0.831	deleterious	N	0.49318886	None	None	N
R/K	0.1106	likely_benign	0.1147	benign	-0.264	Destabilizing	0.06	N	0.134	neutral	N	0.381170076	None	None	N
R/L	0.4378	ambiguous	0.4957	ambiguous	0.416	Stabilizing	0.968	D	0.593	neutral	None	None	None	None	N
R/M	0.4569	ambiguous	0.5001	ambiguous	0.054	Stabilizing	0.999	D	0.554	neutral	None	None	None	None	N
R/N	0.7717	likely_pathogenic	0.8066	pathogenic	0.188	Stabilizing	0.968	D	0.559	neutral	None	None	None	None	N
R/P	0.9537	likely_pathogenic	0.9637	pathogenic	0.212	Stabilizing	0.997	D	0.753	deleterious	None	None	None	None	N
R/Q	0.1458	likely_benign	0.1573	benign	0.027	Stabilizing	0.938	D	0.586	neutral	None	None	None	None	N
R/S	0.6997	likely_pathogenic	0.7401	pathogenic	-0.36	Destabilizing	0.919	D	0.527	neutral	N	0.504288501	None	None	N
R/T	0.4266	ambiguous	0.4653	ambiguous	-0.107	Destabilizing	0.958	D	0.639	neutral	N	0.496266451	None	None	N
R/V	0.5057	ambiguous	0.5395	ambiguous	0.212	Stabilizing	0.991	D	0.636	neutral	None	None	None	None	N
R/W	0.3337	likely_benign	0.399	ambiguous	-0.162	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
R/Y	0.6212	likely_pathogenic	0.6737	pathogenic	0.202	Stabilizing	0.997	D	0.831	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.