TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9951	30076;30077;30078	chr2:178704621;178704620;178704619	chr2:179569348;179569347;179569346
N2AB	9634	29125;29126;29127	chr2:178704621;178704620;178704619	chr2:179569348;179569347;179569346
N2A	8707	26344;26345;26346	chr2:178704621;178704620;178704619	chr2:179569348;179569347;179569346
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-84
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.3624
• 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
I/T	rs1482211815	0.021	0.549	None	0.575	0.231	0.552900881131	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
I/T	rs1482211815	0.021	0.549	None	0.575	0.231	0.552900881131	gnomAD-4.0.0	1.59395E-06	None	None	None	None	N	None	0	2.29474E-05	None	0	0	None	0	0	0	0	0
I/V	None	None	0.002	None	0.243	0.052	0.320256813643	gnomAD-4.0.0	3.42357E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49975E-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
I/A	0.4205	ambiguous	0.5398	ambiguous	-0.78	Destabilizing	0.021	N	0.335	neutral	None	None	None	None	N
I/C	0.8641	likely_pathogenic	0.9199	pathogenic	-0.581	Destabilizing	0.992	D	0.59	neutral	None	None	None	None	N
I/D	0.9205	likely_pathogenic	0.9548	pathogenic	-0.246	Destabilizing	0.85	D	0.687	prob.neutral	None	None	None	None	N
I/E	0.7174	likely_pathogenic	0.8127	pathogenic	-0.341	Destabilizing	0.447	N	0.685	prob.neutral	None	None	None	None	N
I/F	0.3817	ambiguous	0.4731	ambiguous	-0.846	Destabilizing	0.009	N	0.3	neutral	None	None	None	None	N
I/G	0.8739	likely_pathogenic	0.9252	pathogenic	-0.958	Destabilizing	0.617	D	0.671	neutral	None	None	None	None	N
I/H	0.7821	likely_pathogenic	0.8731	pathogenic	-0.298	Destabilizing	0.977	D	0.675	neutral	None	None	None	None	N
I/K	0.4579	ambiguous	0.6038	pathogenic	-0.333	Destabilizing	0.447	N	0.687	prob.neutral	None	None	None	None	N
I/L	0.1981	likely_benign	0.2553	benign	-0.433	Destabilizing	0.099	N	0.315	neutral	None	None	None	None	N
I/M	0.1471	likely_benign	0.1802	benign	-0.33	Destabilizing	0.81	D	0.603	neutral	None	None	None	None	N
I/N	0.6134	likely_pathogenic	0.7337	pathogenic	-0.089	Destabilizing	0.896	D	0.699	prob.neutral	None	None	None	None	N
I/P	0.9522	likely_pathogenic	0.9665	pathogenic	-0.515	Destabilizing	0.92	D	0.7	prob.neutral	None	None	None	None	N
I/Q	0.5875	likely_pathogenic	0.7162	pathogenic	-0.346	Destabilizing	0.127	N	0.552	neutral	None	None	None	None	N
I/R	0.3819	ambiguous	0.5244	ambiguous	0.235	Stabilizing	0.85	D	0.699	prob.neutral	None	None	None	None	N
I/S	0.5018	ambiguous	0.622	pathogenic	-0.568	Destabilizing	0.379	N	0.646	neutral	None	None	None	None	N
I/T	0.2046	likely_benign	0.2812	benign	-0.551	Destabilizing	0.549	D	0.575	neutral	None	None	None	None	N
I/V	0.0806	likely_benign	0.1011	benign	-0.515	Destabilizing	0.002	N	0.243	neutral	None	None	None	None	N
I/W	0.9285	likely_pathogenic	0.9484	pathogenic	-0.851	Destabilizing	0.992	D	0.686	prob.neutral	None	None	None	None	N
I/Y	0.817	likely_pathogenic	0.8732	pathogenic	-0.583	Destabilizing	0.739	D	0.611	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.