TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22309	67150;67151;67152	chr2:178580454;178580453;178580452	chr2:179445181;179445180;179445179
N2AB	20668	62227;62228;62229	chr2:178580454;178580453;178580452	chr2:179445181;179445180;179445179
N2A	19741	59446;59447;59448	chr2:178580454;178580453;178580452	chr2:179445181;179445180;179445179
N2B	13244	39955;39956;39957	chr2:178580454;178580453;178580452	chr2:179445181;179445180;179445179
Novex-1	13369	40330;40331;40332	chr2:178580454;178580453;178580452	chr2:179445181;179445180;179445179
Novex-2	13436	40531;40532;40533	chr2:178580454;178580453;178580452	chr2:179445181;179445180;179445179
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-126
• Domain position: 45
• Structural Position: 122
• Q(SASA): 0.2696
• 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/A	None	None	0.09	N	0.405	0.196	0.301789629655	gnomAD-4.0.0	6.84466E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99701E-07	0	0
D/G	rs1481781346	None	0.324	N	0.317	0.194	0.288352970974	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/G	rs1481781346	None	0.324	N	0.317	0.194	0.288352970974	gnomAD-4.0.0	6.5754E-06	None	None	None	None	N	None	2.4122E-05	0	None	0	0	None	0	0	0	0	0
D/H	rs1204440058	-0.812	0.928	N	0.375	0.208	0.347879110917	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66389E-04
D/H	rs1204440058	-0.812	0.928	N	0.375	0.208	0.347879110917	gnomAD-4.0.0	2.05342E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99705E-07	1.15961E-05	1.65772E-05
D/N	rs1204440058	None	0.324	N	0.365	0.165	0.254244900254	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs1204440058	None	0.324	N	0.365	0.165	0.254244900254	gnomAD-4.0.0	2.47987E-06	None	None	None	None	N	None	4.0078E-05	0	None	0	0	None	0	0	8.47859E-07	0	0
D/V	rs1481781346	None	0.193	N	0.431	0.255	0.306695030598	gnomAD-4.0.0	4.10679E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39821E-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	0.2725	likely_benign	0.287	benign	0.022	Stabilizing	0.09	N	0.405	neutral	N	0.470104144	None	None	N
D/C	0.7383	likely_pathogenic	0.7565	pathogenic	-0.006	Destabilizing	0.981	D	0.469	neutral	None	None	None	None	N
D/E	0.1603	likely_benign	0.1747	benign	-0.349	Destabilizing	0.001	N	0.224	neutral	N	0.40116692	None	None	N
D/F	0.6693	likely_pathogenic	0.6803	pathogenic	0.755	Stabilizing	0.69	D	0.461	neutral	None	None	None	None	N
D/G	0.4163	ambiguous	0.4408	ambiguous	-0.365	Destabilizing	0.324	N	0.317	neutral	N	0.500773767	None	None	N
D/H	0.3726	ambiguous	0.38	ambiguous	0.623	Stabilizing	0.928	D	0.375	neutral	N	0.468181346	None	None	N
D/I	0.3631	ambiguous	0.3727	ambiguous	1.044	Stabilizing	0.241	N	0.404	neutral	None	None	None	None	N
D/K	0.5888	likely_pathogenic	0.595	pathogenic	0.145	Stabilizing	0.241	N	0.319	neutral	None	None	None	None	N
D/L	0.4311	ambiguous	0.4348	ambiguous	1.044	Stabilizing	0.001	N	0.296	neutral	None	None	None	None	N
D/M	0.6329	likely_pathogenic	0.6394	pathogenic	1.178	Stabilizing	0.054	N	0.392	neutral	None	None	None	None	N
D/N	0.1656	likely_benign	0.1752	benign	-0.571	Destabilizing	0.324	N	0.365	neutral	N	0.425505218	None	None	N
D/P	0.9514	likely_pathogenic	0.9529	pathogenic	0.731	Stabilizing	0.818	D	0.346	neutral	None	None	None	None	N
D/Q	0.3937	ambiguous	0.404	ambiguous	-0.354	Destabilizing	0.527	D	0.343	neutral	None	None	None	None	N
D/R	0.5928	likely_pathogenic	0.594	pathogenic	0.377	Stabilizing	0.69	D	0.396	neutral	None	None	None	None	N
D/S	0.1967	likely_benign	0.2	benign	-0.776	Destabilizing	0.241	N	0.323	neutral	None	None	None	None	N
D/T	0.286	likely_benign	0.2896	benign	-0.437	Destabilizing	0.388	N	0.324	neutral	None	None	None	None	N
D/V	0.2282	likely_benign	0.2335	benign	0.731	Stabilizing	0.193	N	0.431	neutral	N	0.4518651	None	None	N
D/W	0.9032	likely_pathogenic	0.902	pathogenic	0.95	Stabilizing	0.981	D	0.504	neutral	None	None	None	None	N
D/Y	0.3203	likely_benign	0.3298	benign	1.038	Stabilizing	0.912	D	0.473	neutral	N	0.468797422	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.