TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23367	70324;70325;70326	chr2:178576033;178576032;178576031	chr2:179440760;179440759;179440758
N2AB	21726	65401;65402;65403	chr2:178576033;178576032;178576031	chr2:179440760;179440759;179440758
N2A	20799	62620;62621;62622	chr2:178576033;178576032;178576031	chr2:179440760;179440759;179440758
N2B	14302	43129;43130;43131	chr2:178576033;178576032;178576031	chr2:179440760;179440759;179440758
Novex-1	14427	43504;43505;43506	chr2:178576033;178576032;178576031	chr2:179440760;179440759;179440758
Novex-2	14494	43705;43706;43707	chr2:178576033;178576032;178576031	chr2:179440760;179440759;179440758
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-129
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.3393
• 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
P/L	None	None	0.999	N	0.776	0.421	0.852004672353	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
P/A	0.3311	likely_benign	0.3788	ambiguous	-1.148	Destabilizing	0.992	D	0.573	neutral	D	0.526784146	None	None	I
P/C	0.9267	likely_pathogenic	0.9473	pathogenic	-0.759	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/D	0.9408	likely_pathogenic	0.9529	pathogenic	-0.895	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	I
P/E	0.8722	likely_pathogenic	0.901	pathogenic	-0.855	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	I
P/F	0.961	likely_pathogenic	0.9717	pathogenic	-0.729	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
P/G	0.7703	likely_pathogenic	0.8124	pathogenic	-1.479	Destabilizing	0.997	D	0.706	prob.neutral	None	None	None	None	I
P/H	0.7717	likely_pathogenic	0.8142	pathogenic	-0.923	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
P/I	0.8817	likely_pathogenic	0.916	pathogenic	-0.336	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
P/K	0.8812	likely_pathogenic	0.904	pathogenic	-0.971	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	I
P/L	0.5497	ambiguous	0.6153	pathogenic	-0.336	Destabilizing	0.999	D	0.776	deleterious	N	0.50518939	None	None	I
P/M	0.8339	likely_pathogenic	0.8707	pathogenic	-0.374	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
P/N	0.8335	likely_pathogenic	0.8776	pathogenic	-0.9	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
P/Q	0.7148	likely_pathogenic	0.7626	pathogenic	-0.978	Destabilizing	0.999	D	0.812	deleterious	N	0.488829427	None	None	I
P/R	0.7776	likely_pathogenic	0.8163	pathogenic	-0.543	Destabilizing	0.999	D	0.795	deleterious	N	0.515297716	None	None	I
P/S	0.5157	ambiguous	0.579	pathogenic	-1.418	Destabilizing	0.957	D	0.428	neutral	D	0.522301046	None	None	I
P/T	0.4085	ambiguous	0.4829	ambiguous	-1.259	Destabilizing	0.998	D	0.728	prob.delet.	N	0.512486697	None	None	I
P/V	0.7456	likely_pathogenic	0.8051	pathogenic	-0.572	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
P/W	0.9801	likely_pathogenic	0.9847	pathogenic	-0.968	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
P/Y	0.9447	likely_pathogenic	0.9573	pathogenic	-0.627	Destabilizing	1.0	D	0.803	deleterious	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.