TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13828	41707;41708;41709	chr2:178636089;178636088;178636087	chr2:179500816;179500815;179500814
N2AB	12187	36784;36785;36786	chr2:178636089;178636088;178636087	chr2:179500816;179500815;179500814
N2A	11260	34003;34004;34005	chr2:178636089;178636088;178636087	chr2:179500816;179500815;179500814
N2B	4763	14512;14513;14514	chr2:178636089;178636088;178636087	chr2:179500816;179500815;179500814
Novex-1	4888	14887;14888;14889	chr2:178636089;178636088;178636087	chr2:179500816;179500815;179500814
Novex-2	4955	15088;15089;15090	chr2:178636089;178636088;178636087	chr2:179500816;179500815;179500814
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-88
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.3251
• 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
P/S	rs748565404	-1.502	0.784	N	0.45	0.163	0.15556083564	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs748565404	-1.502	0.784	N	0.45	0.163	0.15556083564	gnomAD-4.0.0	6.58137E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47132E-05	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
P/A	0.1752	likely_benign	0.1742	benign	-1.08	Destabilizing	0.244	N	0.329	neutral	N	0.347872504	None	None	I
P/C	0.8204	likely_pathogenic	0.8088	pathogenic	-0.896	Destabilizing	0.981	D	0.505	neutral	None	None	None	None	I
P/D	0.8638	likely_pathogenic	0.8697	pathogenic	-0.721	Destabilizing	0.936	D	0.491	neutral	None	None	None	None	I
P/E	0.6577	likely_pathogenic	0.6661	pathogenic	-0.737	Destabilizing	0.936	D	0.465	neutral	None	None	None	None	I
P/F	0.8536	likely_pathogenic	0.866	pathogenic	-0.833	Destabilizing	0.704	D	0.547	neutral	None	None	None	None	I
P/G	0.679	likely_pathogenic	0.6777	pathogenic	-1.359	Destabilizing	0.936	D	0.498	neutral	None	None	None	None	I
P/H	0.4956	ambiguous	0.4832	ambiguous	-0.829	Destabilizing	0.995	D	0.477	neutral	None	None	None	None	I
P/I	0.6659	likely_pathogenic	0.6751	pathogenic	-0.438	Destabilizing	0.001	N	0.251	neutral	None	None	None	None	I
P/K	0.6876	likely_pathogenic	0.6827	pathogenic	-0.969	Destabilizing	0.828	D	0.461	neutral	None	None	None	None	I
P/L	0.2815	likely_benign	0.2809	benign	-0.438	Destabilizing	0.002	N	0.284	neutral	N	0.287582016	None	None	I
P/M	0.6647	likely_pathogenic	0.6627	pathogenic	-0.493	Destabilizing	0.893	D	0.535	neutral	None	None	None	None	I
P/N	0.7617	likely_pathogenic	0.767	pathogenic	-0.78	Destabilizing	0.981	D	0.556	neutral	None	None	None	None	I
P/Q	0.4416	ambiguous	0.4373	ambiguous	-0.917	Destabilizing	0.975	D	0.452	neutral	N	0.34040111	None	None	I
P/R	0.4822	ambiguous	0.4678	ambiguous	-0.487	Destabilizing	0.927	D	0.555	neutral	N	0.337215383	None	None	I
P/S	0.3466	ambiguous	0.3432	ambiguous	-1.273	Destabilizing	0.784	D	0.45	neutral	N	0.335707796	None	None	I
P/T	0.2605	likely_benign	0.2601	benign	-1.169	Destabilizing	0.425	N	0.344	neutral	N	0.339848476	None	None	I
P/V	0.5072	ambiguous	0.508	ambiguous	-0.616	Destabilizing	0.013	N	0.229	neutral	None	None	None	None	I
P/W	0.9133	likely_pathogenic	0.9167	pathogenic	-0.983	Destabilizing	0.995	D	0.595	neutral	None	None	None	None	I
P/Y	0.8262	likely_pathogenic	0.8345	pathogenic	-0.688	Destabilizing	0.944	D	0.571	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.