TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8401	25426;25427;25428	chr2:178717673;178717672;178717671	chr2:179582400;179582399;179582398
N2AB	8084	24475;24476;24477	chr2:178717673;178717672;178717671	chr2:179582400;179582399;179582398
N2A	7157	21694;21695;21696	chr2:178717673;178717672;178717671	chr2:179582400;179582399;179582398
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-69
• Domain position: 42
• Structural Position: 69
• Q(SASA): 0.7977
• 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
K/N	rs1172962931	0.276	0.816	N	0.269	0.224	0.206339911435	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
K/N	rs1172962931	0.276	0.816	N	0.269	0.224	0.206339911435	gnomAD-4.0.0	1.59209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43369E-05	0
K/T	rs753121966	0.094	0.216	N	0.355	0.218	0.305086939656	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
K/T	rs753121966	0.094	0.216	N	0.355	0.218	0.305086939656	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	2.28749E-05	None	0	0	None	0	0	0	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	0.29	likely_benign	0.3032	benign	0.036	Stabilizing	0.032	N	0.19	neutral	None	None	None	None	N
K/C	0.7271	likely_pathogenic	0.7389	pathogenic	-0.377	Destabilizing	0.998	D	0.277	neutral	None	None	None	None	N
K/D	0.4636	ambiguous	0.5089	ambiguous	-0.274	Destabilizing	0.855	D	0.367	neutral	None	None	None	None	N
K/E	0.1231	likely_benign	0.1294	benign	-0.278	Destabilizing	0.355	N	0.314	neutral	N	0.496637384	None	None	N
K/F	0.7344	likely_pathogenic	0.7356	pathogenic	-0.267	Destabilizing	0.892	D	0.313	neutral	None	None	None	None	N
K/G	0.391	ambiguous	0.4095	ambiguous	-0.109	Destabilizing	0.549	D	0.367	neutral	None	None	None	None	N
K/H	0.2477	likely_benign	0.2523	benign	-0.231	Destabilizing	0.017	N	0.247	neutral	None	None	None	None	N
K/I	0.3913	ambiguous	0.3871	ambiguous	0.338	Stabilizing	0.061	N	0.349	neutral	N	0.487327254	None	None	N
K/L	0.336	likely_benign	0.35	ambiguous	0.338	Stabilizing	0.001	N	0.253	neutral	None	None	None	None	N
K/M	0.2436	likely_benign	0.2483	benign	-0.075	Destabilizing	0.712	D	0.313	neutral	None	None	None	None	N
K/N	0.3241	likely_benign	0.3405	ambiguous	0.052	Stabilizing	0.816	D	0.269	neutral	N	0.511740122	None	None	N
K/P	0.5122	ambiguous	0.555	ambiguous	0.261	Stabilizing	0.923	D	0.362	neutral	None	None	None	None	N
K/Q	0.1099	likely_benign	0.1099	benign	-0.077	Destabilizing	0.35	N	0.314	neutral	N	0.494559871	None	None	N
K/R	0.0794	likely_benign	0.0793	benign	-0.09	Destabilizing	0.001	N	0.183	neutral	N	0.45542548	None	None	N
K/S	0.3147	likely_benign	0.3319	benign	-0.297	Destabilizing	0.032	N	0.174	neutral	None	None	None	None	N
K/T	0.1496	likely_benign	0.1503	benign	-0.179	Destabilizing	0.216	N	0.355	neutral	N	0.472472445	None	None	N
K/V	0.3483	ambiguous	0.3543	ambiguous	0.261	Stabilizing	0.103	N	0.362	neutral	None	None	None	None	N
K/W	0.6894	likely_pathogenic	0.6852	pathogenic	-0.377	Destabilizing	0.999	D	0.286	neutral	None	None	None	None	N
K/Y	0.5747	likely_pathogenic	0.5909	pathogenic	-0.025	Destabilizing	0.491	N	0.328	neutral	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.