TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25061	75406;75407;75408	chr2:178570951;178570950;178570949	chr2:179435678;179435677;179435676
N2AB	23420	70483;70484;70485	chr2:178570951;178570950;178570949	chr2:179435678;179435677;179435676
N2A	22493	67702;67703;67704	chr2:178570951;178570950;178570949	chr2:179435678;179435677;179435676
N2B	15996	48211;48212;48213	chr2:178570951;178570950;178570949	chr2:179435678;179435677;179435676
Novex-1	16121	48586;48587;48588	chr2:178570951;178570950;178570949	chr2:179435678;179435677;179435676
Novex-2	16188	48787;48788;48789	chr2:178570951;178570950;178570949	chr2:179435678;179435677;179435676
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: Fn3-70
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0915
• 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	rs1455981724	-2.046	0.062	N	0.559	0.226	0.558966020747	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
I/T	rs1455981724	-2.046	0.062	N	0.559	0.226	0.558966020747	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	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
I/A	0.792	likely_pathogenic	0.7846	pathogenic	-1.858	Destabilizing	0.035	N	0.533	neutral	None	None	None	None	N
I/C	0.8481	likely_pathogenic	0.8366	pathogenic	-1.116	Destabilizing	0.824	D	0.573	neutral	None	None	None	None	N
I/D	0.977	likely_pathogenic	0.974	pathogenic	-1.731	Destabilizing	0.555	D	0.651	neutral	None	None	None	None	N
I/E	0.9557	likely_pathogenic	0.9509	pathogenic	-1.49	Destabilizing	0.555	D	0.647	neutral	None	None	None	None	N
I/F	0.7282	likely_pathogenic	0.7201	pathogenic	-0.989	Destabilizing	0.317	N	0.62	neutral	N	0.478570807	None	None	N
I/G	0.9516	likely_pathogenic	0.9487	pathogenic	-2.41	Highly Destabilizing	0.555	D	0.649	neutral	None	None	None	None	N
I/H	0.9411	likely_pathogenic	0.9351	pathogenic	-2.008	Highly Destabilizing	0.935	D	0.61	neutral	None	None	None	None	N
I/K	0.9192	likely_pathogenic	0.9133	pathogenic	-1.082	Destabilizing	0.38	N	0.647	neutral	None	None	None	None	N
I/L	0.2956	likely_benign	0.283	benign	-0.278	Destabilizing	0.004	N	0.394	neutral	N	0.511283471	None	None	N
I/M	0.3047	likely_benign	0.2912	benign	-0.368	Destabilizing	0.012	N	0.403	neutral	N	0.492409101	None	None	N
I/N	0.7619	likely_pathogenic	0.7409	pathogenic	-1.418	Destabilizing	0.484	N	0.663	neutral	N	0.471974215	None	None	N
I/P	0.9752	likely_pathogenic	0.9745	pathogenic	-0.783	Destabilizing	0.555	D	0.661	neutral	None	None	None	None	N
I/Q	0.9266	likely_pathogenic	0.9211	pathogenic	-1.206	Destabilizing	0.555	D	0.661	neutral	None	None	None	None	N
I/R	0.8969	likely_pathogenic	0.8862	pathogenic	-1.084	Destabilizing	0.555	D	0.661	neutral	None	None	None	None	N
I/S	0.787	likely_pathogenic	0.7716	pathogenic	-2.154	Highly Destabilizing	0.117	N	0.597	neutral	N	0.498100743	None	None	N
I/T	0.6043	likely_pathogenic	0.5938	pathogenic	-1.755	Destabilizing	0.062	N	0.559	neutral	N	0.509435244	None	None	N
I/V	0.0596	likely_benign	0.0622	benign	-0.783	Destabilizing	None	N	0.196	neutral	N	0.408503033	None	None	N
I/W	0.9893	likely_pathogenic	0.9886	pathogenic	-1.366	Destabilizing	0.935	D	0.641	neutral	None	None	None	None	N
I/Y	0.9434	likely_pathogenic	0.9357	pathogenic	-0.988	Destabilizing	0.555	D	0.643	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.