TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2446	7561;7562;7563	chr2:178773720;178773719;178773718	chr2:179638447;179638446;179638445
N2AB	2446	7561;7562;7563	chr2:178773720;178773719;178773718	chr2:179638447;179638446;179638445
N2A	2446	7561;7562;7563	chr2:178773720;178773719;178773718	chr2:179638447;179638446;179638445
N2B	2400	7423;7424;7425	chr2:178773720;178773719;178773718	chr2:179638447;179638446;179638445
Novex-1	2400	7423;7424;7425	chr2:178773720;178773719;178773718	chr2:179638447;179638446;179638445
Novex-2	2400	7423;7424;7425	chr2:178773720;178773719;178773718	chr2:179638447;179638446;179638445
Novex-3	2446	7561;7562;7563	chr2:178773720;178773719;178773718	chr2:179638447;179638446;179638445

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-14
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3793
• 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
D/N	None	None	0.001	N	0.264	0.081	0.225902525712	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
D/A	0.1415	likely_benign	0.1334	benign	-0.21	Destabilizing	0.001	N	0.307	neutral	N	0.498196464	None	None	N
D/C	0.6063	likely_pathogenic	0.5838	pathogenic	-0.167	Destabilizing	0.944	D	0.421	neutral	None	None	None	None	N
D/E	0.1416	likely_benign	0.1374	benign	-0.302	Destabilizing	0.002	N	0.167	neutral	N	0.433439697	None	None	N
D/F	0.6443	likely_pathogenic	0.6201	pathogenic	0.09	Stabilizing	0.818	D	0.438	neutral	None	None	None	None	N
D/G	0.1553	likely_benign	0.1471	benign	-0.44	Destabilizing	0.09	N	0.405	neutral	N	0.481664901	None	None	N
D/H	0.277	likely_benign	0.2665	benign	0.38	Stabilizing	0.773	D	0.411	neutral	D	0.532665891	None	None	N
D/I	0.4306	ambiguous	0.3987	ambiguous	0.355	Stabilizing	0.69	D	0.452	neutral	None	None	None	None	N
D/K	0.3621	ambiguous	0.3551	ambiguous	0.303	Stabilizing	0.241	N	0.398	neutral	None	None	None	None	N
D/L	0.4318	ambiguous	0.408	ambiguous	0.355	Stabilizing	0.241	N	0.398	neutral	None	None	None	None	N
D/M	0.5708	likely_pathogenic	0.5388	ambiguous	0.308	Stabilizing	0.981	D	0.418	neutral	None	None	None	None	N
D/N	0.0949	likely_benign	0.0904	benign	-0.236	Destabilizing	0.001	N	0.264	neutral	N	0.496990996	None	None	N
D/P	0.8485	likely_pathogenic	0.8336	pathogenic	0.189	Stabilizing	0.818	D	0.389	neutral	None	None	None	None	N
D/Q	0.3087	likely_benign	0.2968	benign	-0.151	Destabilizing	0.241	N	0.377	neutral	None	None	None	None	N
D/R	0.4038	ambiguous	0.3938	ambiguous	0.589	Stabilizing	0.69	D	0.413	neutral	None	None	None	None	N
D/S	0.094	likely_benign	0.0899	benign	-0.313	Destabilizing	0.008	N	0.201	neutral	None	None	None	None	N
D/T	0.1993	likely_benign	0.1876	benign	-0.121	Destabilizing	0.241	N	0.393	neutral	None	None	None	None	N
D/V	0.2577	likely_benign	0.2402	benign	0.189	Stabilizing	0.193	N	0.397	neutral	D	0.532665891	None	None	N
D/W	0.8991	likely_pathogenic	0.8911	pathogenic	0.268	Stabilizing	0.981	D	0.509	neutral	None	None	None	None	N
D/Y	0.3209	likely_benign	0.303	benign	0.342	Stabilizing	0.912	D	0.438	neutral	D	0.53383573	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.