TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13784	41575;41576;41577	chr2:178636221;178636220;178636219	chr2:179500948;179500947;179500946
N2AB	12143	36652;36653;36654	chr2:178636221;178636220;178636219	chr2:179500948;179500947;179500946
N2A	11216	33871;33872;33873	chr2:178636221;178636220;178636219	chr2:179500948;179500947;179500946
N2B	4719	14380;14381;14382	chr2:178636221;178636220;178636219	chr2:179500948;179500947;179500946
Novex-1	4844	14755;14756;14757	chr2:178636221;178636220;178636219	chr2:179500948;179500947;179500946
Novex-2	4911	14956;14957;14958	chr2:178636221;178636220;178636219	chr2:179500948;179500947;179500946
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-88
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.515
• 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	None	None	0.638	D	0.54	0.248	0.274366138417	gnomAD-4.0.0	3.32251E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.03776E-05	0
K/R	None	None	0.002	N	0.407	0.144	0.376039117802	gnomAD-4.0.0	1.66562E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.52527E-05	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	0.7834	likely_pathogenic	0.8929	pathogenic	-0.302	Destabilizing	0.25	N	0.585	neutral	None	None	None	None	N
K/C	0.9204	likely_pathogenic	0.9521	pathogenic	-0.31	Destabilizing	0.982	D	0.788	deleterious	None	None	None	None	N
K/D	0.8764	likely_pathogenic	0.9362	pathogenic	0.137	Stabilizing	0.7	D	0.605	neutral	None	None	None	None	N
K/E	0.4799	ambiguous	0.6984	pathogenic	0.206	Stabilizing	0.201	N	0.524	neutral	D	0.618322593	None	None	N
K/F	0.973	likely_pathogenic	0.9889	pathogenic	-0.102	Destabilizing	0.947	D	0.77	deleterious	None	None	None	None	N
K/G	0.8298	likely_pathogenic	0.9067	pathogenic	-0.619	Destabilizing	0.399	N	0.598	neutral	None	None	None	None	N
K/H	0.5461	ambiguous	0.6339	pathogenic	-0.899	Destabilizing	0.898	D	0.659	prob.neutral	None	None	None	None	N
K/I	0.8735	likely_pathogenic	0.9531	pathogenic	0.493	Stabilizing	0.781	D	0.811	deleterious	D	0.597379448	None	None	N
K/L	0.8203	likely_pathogenic	0.902	pathogenic	0.493	Stabilizing	0.399	N	0.598	neutral	None	None	None	None	N
K/M	0.7113	likely_pathogenic	0.8441	pathogenic	0.328	Stabilizing	0.947	D	0.653	prob.neutral	None	None	None	None	N
K/N	0.7067	likely_pathogenic	0.8423	pathogenic	-0.071	Destabilizing	0.638	D	0.54	neutral	D	0.595714887	None	None	N
K/P	0.9826	likely_pathogenic	0.9907	pathogenic	0.259	Stabilizing	0.826	D	0.679	prob.neutral	None	None	None	None	N
K/Q	0.2879	likely_benign	0.4025	ambiguous	-0.193	Destabilizing	0.015	N	0.337	neutral	N	0.521446216	None	None	N
K/R	0.112	likely_benign	0.1327	benign	-0.362	Destabilizing	0.002	N	0.407	neutral	N	0.5206164	None	None	N
K/S	0.7839	likely_pathogenic	0.8835	pathogenic	-0.698	Destabilizing	0.25	N	0.531	neutral	None	None	None	None	N
K/T	0.568	likely_pathogenic	0.7344	pathogenic	-0.441	Destabilizing	0.638	D	0.609	neutral	D	0.578468739	None	None	N
K/V	0.822	likely_pathogenic	0.917	pathogenic	0.259	Stabilizing	0.7	D	0.678	prob.neutral	None	None	None	None	N
K/W	0.9609	likely_pathogenic	0.9803	pathogenic	0.002	Stabilizing	0.982	D	0.767	deleterious	None	None	None	None	N
K/Y	0.9194	likely_pathogenic	0.9601	pathogenic	0.286	Stabilizing	0.826	D	0.801	deleterious	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.