TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22959	69100;69101;69102	chr2:178577460;178577459;178577458	chr2:179442187;179442186;179442185
N2AB	21318	64177;64178;64179	chr2:178577460;178577459;178577458	chr2:179442187;179442186;179442185
N2A	20391	61396;61397;61398	chr2:178577460;178577459;178577458	chr2:179442187;179442186;179442185
N2B	13894	41905;41906;41907	chr2:178577460;178577459;178577458	chr2:179442187;179442186;179442185
Novex-1	14019	42280;42281;42282	chr2:178577460;178577459;178577458	chr2:179442187;179442186;179442185
Novex-2	14086	42481;42482;42483	chr2:178577460;178577459;178577458	chr2:179442187;179442186;179442185
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-128
• Domain position: 10
• Structural Position: 18
• Q(SASA): 0.9166
• 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
K/T	None	None	0.997	N	0.596	0.437	0.477298106951	gnomAD-4.0.0	1.62294E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.0722E-05

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	0.7355	likely_pathogenic	0.5482	ambiguous	-0.068	Destabilizing	0.985	D	0.626	neutral	None	None	None	None	I
K/C	0.7767	likely_pathogenic	0.7251	pathogenic	-0.349	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
K/D	0.9355	likely_pathogenic	0.8579	pathogenic	0.12	Stabilizing	0.998	D	0.626	neutral	None	None	None	None	I
K/E	0.5467	ambiguous	0.378	ambiguous	0.153	Stabilizing	0.98	D	0.631	neutral	D	0.525824141	None	None	I
K/F	0.885	likely_pathogenic	0.8173	pathogenic	-0.157	Destabilizing	0.996	D	0.666	neutral	None	None	None	None	I
K/G	0.8119	likely_pathogenic	0.7024	pathogenic	-0.301	Destabilizing	0.993	D	0.588	neutral	None	None	None	None	I
K/H	0.3652	ambiguous	0.2868	benign	-0.496	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	I
K/I	0.7158	likely_pathogenic	0.5454	ambiguous	0.474	Stabilizing	0.989	D	0.674	neutral	N	0.490531856	None	None	I
K/L	0.5652	likely_pathogenic	0.4354	ambiguous	0.474	Stabilizing	0.971	D	0.623	neutral	None	None	None	None	I
K/M	0.413	ambiguous	0.3137	benign	0.147	Stabilizing	0.931	D	0.551	neutral	None	None	None	None	I
K/N	0.8007	likely_pathogenic	0.6698	pathogenic	0.023	Stabilizing	0.997	D	0.607	neutral	N	0.519340885	None	None	I
K/P	0.8312	likely_pathogenic	0.7055	pathogenic	0.322	Stabilizing	0.999	D	0.637	neutral	None	None	None	None	I
K/Q	0.2394	likely_benign	0.1686	benign	-0.089	Destabilizing	0.994	D	0.628	neutral	N	0.482325422	None	None	I
K/R	0.0751	likely_benign	0.0728	benign	-0.129	Destabilizing	0.135	N	0.288	neutral	N	0.478686342	None	None	I
K/S	0.815	likely_pathogenic	0.6628	pathogenic	-0.487	Destabilizing	0.993	D	0.619	neutral	None	None	None	None	I
K/T	0.5401	ambiguous	0.3306	benign	-0.291	Destabilizing	0.997	D	0.596	neutral	N	0.521322398	None	None	I
K/V	0.6667	likely_pathogenic	0.4874	ambiguous	0.322	Stabilizing	0.971	D	0.589	neutral	None	None	None	None	I
K/W	0.8452	likely_pathogenic	0.7761	pathogenic	-0.164	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
K/Y	0.7776	likely_pathogenic	0.6978	pathogenic	0.176	Stabilizing	0.999	D	0.659	neutral	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.