TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30245	90958;90959;90960	chr2:178552167;178552166;178552165	chr2:179416894;179416893;179416892
N2AB	28604	86035;86036;86037	chr2:178552167;178552166;178552165	chr2:179416894;179416893;179416892
N2A	27677	83254;83255;83256	chr2:178552167;178552166;178552165	chr2:179416894;179416893;179416892
N2B	21180	63763;63764;63765	chr2:178552167;178552166;178552165	chr2:179416894;179416893;179416892
Novex-1	21305	64138;64139;64140	chr2:178552167;178552166;178552165	chr2:179416894;179416893;179416892
Novex-2	21372	64339;64340;64341	chr2:178552167;178552166;178552165	chr2:179416894;179416893;179416892
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-108
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.173
• 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
S/L	rs1407888645	None	1.0	N	0.786	0.456	0.814184237618	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85817E-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
S/A	0.172	likely_benign	0.1711	benign	-0.878	Destabilizing	0.997	D	0.52	neutral	N	0.487581071	None	None	N
S/C	0.1852	likely_benign	0.1803	benign	-0.674	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
S/D	0.8715	likely_pathogenic	0.849	pathogenic	-1.023	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
S/E	0.843	likely_pathogenic	0.822	pathogenic	-0.891	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
S/F	0.4973	ambiguous	0.4436	ambiguous	-0.794	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
S/G	0.2096	likely_benign	0.2155	benign	-1.234	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
S/H	0.5273	ambiguous	0.4979	ambiguous	-1.562	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
S/I	0.5503	ambiguous	0.4828	ambiguous	0.003	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
S/K	0.8894	likely_pathogenic	0.8795	pathogenic	-0.394	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
S/L	0.2813	likely_benign	0.2484	benign	0.003	Stabilizing	1.0	D	0.786	deleterious	N	0.504711048	None	None	N
S/M	0.406	ambiguous	0.3691	ambiguous	0.05	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
S/N	0.4761	ambiguous	0.4341	ambiguous	-0.852	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
S/P	0.9875	likely_pathogenic	0.9862	pathogenic	-0.256	Destabilizing	1.0	D	0.838	deleterious	D	0.546959945	None	None	N
S/Q	0.7038	likely_pathogenic	0.6791	pathogenic	-0.778	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
S/R	0.8402	likely_pathogenic	0.8173	pathogenic	-0.571	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
S/T	0.1277	likely_benign	0.1277	benign	-0.667	Destabilizing	0.999	D	0.548	neutral	N	0.509344817	None	None	N
S/V	0.4934	ambiguous	0.449	ambiguous	-0.256	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
S/W	0.6631	likely_pathogenic	0.6003	pathogenic	-0.907	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
S/Y	0.4652	ambiguous	0.4127	ambiguous	-0.529	Destabilizing	1.0	D	0.907	deleterious	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.