TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19333	58222;58223;58224	chr2:178594497;178594496;178594495	chr2:179459224;179459223;179459222
N2AB	17692	53299;53300;53301	chr2:178594497;178594496;178594495	chr2:179459224;179459223;179459222
N2A	16765	50518;50519;50520	chr2:178594497;178594496;178594495	chr2:179459224;179459223;179459222
N2B	10268	31027;31028;31029	chr2:178594497;178594496;178594495	chr2:179459224;179459223;179459222
Novex-1	10393	31402;31403;31404	chr2:178594497;178594496;178594495	chr2:179459224;179459223;179459222
Novex-2	10460	31603;31604;31605	chr2:178594497;178594496;178594495	chr2:179459224;179459223;179459222
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: Fn3-28
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.3601
• 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/N	rs777279726	-0.232	0.351	N	0.355	0.155	0.17258766438	gnomAD-4.0.0	1.59211E-06	None	None	None	None	N	None	0	0	None	0	2.77716E-05	None	0	0	0	0	0
K/R	rs1469122729	-0.43	0.001	N	0.182	0.115	0.134241683229	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
K/R	rs1469122729	-0.43	0.001	N	0.182	0.115	0.134241683229	gnomAD-4.0.0	3.18422E-06	None	None	None	None	N	None	0	0	None	0	2.77685E-05	None	0	0	2.85992E-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	0.4496	ambiguous	0.3583	ambiguous	-0.256	Destabilizing	0.129	N	0.414	neutral	None	None	None	None	N
K/C	0.7095	likely_pathogenic	0.6688	pathogenic	-0.38	Destabilizing	0.983	D	0.566	neutral	None	None	None	None	N
K/D	0.8056	likely_pathogenic	0.7021	pathogenic	0.048	Stabilizing	0.418	N	0.489	neutral	None	None	None	None	N
K/E	0.345	ambiguous	0.2377	benign	0.102	Stabilizing	0.351	N	0.338	neutral	N	0.42421906	None	None	N
K/F	0.8535	likely_pathogenic	0.776	pathogenic	-0.169	Destabilizing	0.836	D	0.575	neutral	None	None	None	None	N
K/G	0.6845	likely_pathogenic	0.5827	pathogenic	-0.556	Destabilizing	0.264	N	0.51	neutral	None	None	None	None	N
K/H	0.3667	ambiguous	0.3191	benign	-0.925	Destabilizing	0.836	D	0.553	neutral	None	None	None	None	N
K/I	0.4228	ambiguous	0.3259	benign	0.482	Stabilizing	0.003	N	0.493	neutral	N	0.494796652	None	None	N
K/L	0.4348	ambiguous	0.3617	ambiguous	0.482	Stabilizing	0.129	N	0.439	neutral	None	None	None	None	N
K/M	0.3315	likely_benign	0.2482	benign	0.345	Stabilizing	0.836	D	0.55	neutral	None	None	None	None	N
K/N	0.6592	likely_pathogenic	0.5264	ambiguous	-0.107	Destabilizing	0.351	N	0.355	neutral	N	0.495911373	None	None	N
K/P	0.5442	ambiguous	0.5	ambiguous	0.267	Stabilizing	0.836	D	0.583	neutral	None	None	None	None	N
K/Q	0.1747	likely_benign	0.1474	benign	-0.272	Destabilizing	0.351	N	0.415	neutral	N	0.450581728	None	None	N
K/R	0.0756	likely_benign	0.0736	benign	-0.383	Destabilizing	0.001	N	0.182	neutral	N	0.4010197	None	None	N
K/S	0.6295	likely_pathogenic	0.5181	ambiguous	-0.712	Destabilizing	0.01	N	0.226	neutral	None	None	None	None	N
K/T	0.2714	likely_benign	0.1873	benign	-0.478	Destabilizing	0.101	N	0.415	neutral	N	0.450157654	None	None	N
K/V	0.3645	ambiguous	0.2882	benign	0.267	Stabilizing	0.004	N	0.411	neutral	None	None	None	None	N
K/W	0.8146	likely_pathogenic	0.7399	pathogenic	-0.07	Destabilizing	0.983	D	0.584	neutral	None	None	None	None	N
K/Y	0.7265	likely_pathogenic	0.635	pathogenic	0.24	Stabilizing	0.94	D	0.577	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.