TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3824	11695;11696;11697	chr2:178741763;178741762;178741761	chr2:179606490;179606489;179606488
N2AB	3507	10744;10745;10746	chr2:178741763;178741762;178741761	chr2:179606490;179606489;179606488
N2A	None	None	chr2:None	chr2:None
N2B	3461	10606;10607;10608	chr2:178741763;178741762;178741761	chr2:179606490;179606489;179606488
Novex-1	3586	10981;10982;10983	chr2:178741763;178741762;178741761	chr2:179606490;179606489;179606488
Novex-2	3653	11182;11183;11184	chr2:178741763;178741762;178741761	chr2:179606490;179606489;179606488
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-27
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.3522
• 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/E	None	None	0.193	N	0.238	0.161	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.5734	likely_pathogenic	0.4435	ambiguous	-0.422	Destabilizing	0.116	N	0.317	neutral	None	None	None	None	N
K/C	0.839	likely_pathogenic	0.7496	pathogenic	-0.481	Destabilizing	0.005	N	0.311	neutral	None	None	None	None	N
K/D	0.6808	likely_pathogenic	0.5482	ambiguous	0.019	Stabilizing	0.388	N	0.346	neutral	None	None	None	None	N
K/E	0.1815	likely_benign	0.1458	benign	0.085	Stabilizing	0.193	N	0.238	neutral	N	0.48237772	None	None	N
K/F	0.9234	likely_pathogenic	0.8603	pathogenic	-0.309	Destabilizing	0.818	D	0.364	neutral	None	None	None	None	N
K/G	0.5988	likely_pathogenic	0.4622	ambiguous	-0.735	Destabilizing	0.388	N	0.303	neutral	None	None	None	None	N
K/H	0.4336	ambiguous	0.3393	benign	-1.069	Destabilizing	0.818	D	0.365	neutral	None	None	None	None	N
K/I	0.6697	likely_pathogenic	0.5707	pathogenic	0.361	Stabilizing	0.627	D	0.375	neutral	N	0.512350285	None	None	N
K/L	0.6199	likely_pathogenic	0.5118	ambiguous	0.361	Stabilizing	0.388	N	0.307	neutral	None	None	None	None	N
K/M	0.4289	ambiguous	0.3453	ambiguous	0.298	Stabilizing	0.932	D	0.365	neutral	None	None	None	None	N
K/N	0.5074	ambiguous	0.3819	ambiguous	-0.205	Destabilizing	0.324	N	0.251	neutral	N	0.51191043	None	None	N
K/P	0.9502	likely_pathogenic	0.9105	pathogenic	0.131	Stabilizing	0.818	D	0.371	neutral	None	None	None	None	N
K/Q	0.1715	likely_benign	0.1369	benign	-0.374	Destabilizing	0.324	N	0.312	neutral	N	0.476504473	None	None	N
K/R	0.09	likely_benign	0.0829	benign	-0.4	Destabilizing	0.001	N	0.077	neutral	N	0.485735202	None	None	N
K/S	0.5433	ambiguous	0.4096	ambiguous	-0.869	Destabilizing	0.004	N	0.074	neutral	None	None	None	None	N
K/T	0.2848	likely_benign	0.2145	benign	-0.612	Destabilizing	0.193	N	0.302	neutral	N	0.463041295	None	None	N
K/V	0.6345	likely_pathogenic	0.5327	ambiguous	0.131	Stabilizing	0.388	N	0.335	neutral	None	None	None	None	N
K/W	0.872	likely_pathogenic	0.7871	pathogenic	-0.171	Destabilizing	0.981	D	0.392	neutral	None	None	None	None	N
K/Y	0.8018	likely_pathogenic	0.7109	pathogenic	0.132	Stabilizing	0.818	D	0.356	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.