TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24719	74380;74381;74382	chr2:178571977;178571976;178571975	chr2:179436704;179436703;179436702
N2AB	23078	69457;69458;69459	chr2:178571977;178571976;178571975	chr2:179436704;179436703;179436702
N2A	22151	66676;66677;66678	chr2:178571977;178571976;178571975	chr2:179436704;179436703;179436702
N2B	15654	47185;47186;47187	chr2:178571977;178571976;178571975	chr2:179436704;179436703;179436702
Novex-1	15779	47560;47561;47562	chr2:178571977;178571976;178571975	chr2:179436704;179436703;179436702
Novex-2	15846	47761;47762;47763	chr2:178571977;178571976;178571975	chr2:179436704;179436703;179436702
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-133
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.7129
• 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	rs1708348947	None	0.935	N	0.667	0.163	0.141422826196	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs1708348947	None	0.935	N	0.667	0.163	0.141422826196	gnomAD-4.0.0	6.57981E-06	None	None	None	None	N	None	2.41604E-05	0	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	0.5685	likely_pathogenic	0.6119	pathogenic	-0.106	Destabilizing	0.916	D	0.597	neutral	None	None	None	None	N
K/C	0.7689	likely_pathogenic	0.7805	pathogenic	-0.458	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
K/D	0.6675	likely_pathogenic	0.7174	pathogenic	0.059	Stabilizing	0.033	N	0.331	neutral	None	None	None	None	N
K/E	0.2851	likely_benign	0.3264	benign	0.128	Stabilizing	0.805	D	0.524	neutral	N	0.464038523	None	None	N
K/F	0.8793	likely_pathogenic	0.8922	pathogenic	-0.054	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
K/G	0.6704	likely_pathogenic	0.6989	pathogenic	-0.371	Destabilizing	0.916	D	0.565	neutral	None	None	None	None	N
K/H	0.2833	likely_benign	0.283	benign	-0.477	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
K/I	0.5828	likely_pathogenic	0.6342	pathogenic	0.539	Stabilizing	0.983	D	0.713	prob.delet.	N	0.485219085	None	None	N
K/L	0.5319	ambiguous	0.5561	ambiguous	0.539	Stabilizing	0.987	D	0.611	neutral	None	None	None	None	N
K/M	0.4536	ambiguous	0.4751	ambiguous	0.04	Stabilizing	0.999	D	0.674	neutral	None	None	None	None	N
K/N	0.5356	ambiguous	0.5751	pathogenic	-0.14	Destabilizing	0.935	D	0.667	neutral	N	0.494014714	None	None	N
K/P	0.7726	likely_pathogenic	0.826	pathogenic	0.353	Stabilizing	0.987	D	0.684	prob.neutral	None	None	None	None	N
K/Q	0.1528	likely_benign	0.1573	benign	-0.172	Destabilizing	0.983	D	0.679	prob.neutral	N	0.47344744	None	None	N
K/R	0.0798	likely_benign	0.0792	benign	-0.182	Destabilizing	0.944	D	0.57	neutral	N	0.451282657	None	None	N
K/S	0.5181	ambiguous	0.5544	ambiguous	-0.628	Destabilizing	0.916	D	0.575	neutral	None	None	None	None	N
K/T	0.2776	likely_benign	0.307	benign	-0.384	Destabilizing	0.967	D	0.651	neutral	N	0.493742568	None	None	N
K/V	0.5028	ambiguous	0.553	ambiguous	0.353	Stabilizing	0.987	D	0.662	neutral	None	None	None	None	N
K/W	0.8457	likely_pathogenic	0.8538	pathogenic	-0.081	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
K/Y	0.733	likely_pathogenic	0.7485	pathogenic	0.247	Stabilizing	0.996	D	0.691	prob.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.