TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33499	100720;100721;100722	chr2:178536252;178536251;178536250	chr2:179400979;179400978;179400977
N2AB	31858	95797;95798;95799	chr2:178536252;178536251;178536250	chr2:179400979;179400978;179400977
N2A	30931	93016;93017;93018	chr2:178536252;178536251;178536250	chr2:179400979;179400978;179400977
N2B	24434	73525;73526;73527	chr2:178536252;178536251;178536250	chr2:179400979;179400978;179400977
Novex-1	24559	73900;73901;73902	chr2:178536252;178536251;178536250	chr2:179400979;179400978;179400977
Novex-2	24626	74101;74102;74103	chr2:178536252;178536251;178536250	chr2:179400979;179400978;179400977
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-158
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5046
• 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
K/N	rs1242533868	0.323	0.998	N	0.689	0.319	0.362361684037	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	1.67654E-04	None	0	None	0	0	0
K/N	rs1242533868	0.323	0.998	N	0.689	0.319	0.362361684037	gnomAD-4.0.0	3.18389E-06	None	None	None	None	I	None	0	0	None	0	5.5497E-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
K/A	0.6515	likely_pathogenic	0.8052	pathogenic	-0.304	Destabilizing	0.995	D	0.6	neutral	None	None	None	None	I
K/C	0.8864	likely_pathogenic	0.9206	pathogenic	-0.206	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
K/D	0.9062	likely_pathogenic	0.9581	pathogenic	-0.161	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
K/E	0.4687	ambiguous	0.6884	pathogenic	-0.091	Destabilizing	0.958	D	0.557	neutral	N	0.473808958	None	None	I
K/F	0.9461	likely_pathogenic	0.9698	pathogenic	-0.093	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
K/G	0.8026	likely_pathogenic	0.8871	pathogenic	-0.623	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	I
K/H	0.5876	likely_pathogenic	0.6752	pathogenic	-0.994	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
K/I	0.5558	ambiguous	0.727	pathogenic	0.5	Stabilizing	0.98	D	0.717	prob.delet.	N	0.443061976	None	None	I
K/L	0.6186	likely_pathogenic	0.752	pathogenic	0.5	Stabilizing	0.954	D	0.597	neutral	None	None	None	None	I
K/M	0.521	ambiguous	0.6801	pathogenic	0.306	Stabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
K/N	0.8114	likely_pathogenic	0.9069	pathogenic	-0.168	Destabilizing	0.998	D	0.689	prob.neutral	N	0.517061089	None	None	I
K/P	0.942	likely_pathogenic	0.9591	pathogenic	0.262	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
K/Q	0.2379	likely_benign	0.3409	ambiguous	-0.25	Destabilizing	0.97	D	0.687	prob.neutral	N	0.502977071	None	None	I
K/R	0.0977	likely_benign	0.1017	benign	-0.505	Destabilizing	0.042	N	0.198	neutral	N	0.460975733	None	None	I
K/S	0.7374	likely_pathogenic	0.864	pathogenic	-0.661	Destabilizing	0.995	D	0.611	neutral	None	None	None	None	I
K/T	0.3804	ambiguous	0.5679	pathogenic	-0.412	Destabilizing	0.994	D	0.67	neutral	N	0.435634572	None	None	I
K/V	0.5306	ambiguous	0.6872	pathogenic	0.262	Stabilizing	0.965	D	0.682	prob.neutral	None	None	None	None	I
K/W	0.9239	likely_pathogenic	0.9464	pathogenic	-0.052	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
K/Y	0.899	likely_pathogenic	0.9327	pathogenic	0.22	Stabilizing	0.99	D	0.701	prob.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.