TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17658	53197;53198;53199	chr2:178607815;178607814;178607813	chr2:179472542;179472541;179472540
N2AB	16017	48274;48275;48276	chr2:178607815;178607814;178607813	chr2:179472542;179472541;179472540
N2A	15090	45493;45494;45495	chr2:178607815;178607814;178607813	chr2:179472542;179472541;179472540
N2B	8593	26002;26003;26004	chr2:178607815;178607814;178607813	chr2:179472542;179472541;179472540
Novex-1	8718	26377;26378;26379	chr2:178607815;178607814;178607813	chr2:179472542;179472541;179472540
Novex-2	8785	26578;26579;26580	chr2:178607815;178607814;178607813	chr2:179472542;179472541;179472540
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-16
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.2841
• 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
T/K	rs1576367047	None	0.999	N	0.853	0.37	0.36893422563	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/K	rs1576367047	None	0.999	N	0.853	0.37	0.36893422563	gnomAD-4.0.0	6.57955E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4721E-05	0	0
T/S	None	None	0.997	N	0.754	0.202	0.144782658237	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
T/A	0.371	ambiguous	0.317	benign	-0.935	Destabilizing	0.997	D	0.737	deleterious	N	0.481624206	None	None	N
T/C	0.7476	likely_pathogenic	0.7149	pathogenic	-0.693	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/D	0.9232	likely_pathogenic	0.9208	pathogenic	-0.784	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
T/E	0.9272	likely_pathogenic	0.9309	pathogenic	-0.664	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
T/F	0.8744	likely_pathogenic	0.8395	pathogenic	-0.542	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
T/G	0.6187	likely_pathogenic	0.5994	pathogenic	-1.314	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
T/H	0.9364	likely_pathogenic	0.9314	pathogenic	-1.481	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
T/I	0.6122	likely_pathogenic	0.5601	ambiguous	0.028	Stabilizing	0.999	D	0.839	deleterious	N	0.468425623	None	None	N
T/K	0.9335	likely_pathogenic	0.9295	pathogenic	-0.823	Destabilizing	0.999	D	0.853	deleterious	N	0.460896354	None	None	N
T/L	0.3639	ambiguous	0.3318	benign	0.028	Stabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
T/M	0.2728	likely_benign	0.234	benign	0.051	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
T/N	0.6547	likely_pathogenic	0.6466	pathogenic	-1.115	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
T/P	0.7451	likely_pathogenic	0.7646	pathogenic	-0.259	Destabilizing	0.999	D	0.818	deleterious	N	0.454802965	None	None	N
T/Q	0.9036	likely_pathogenic	0.8994	pathogenic	-1.029	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
T/R	0.9242	likely_pathogenic	0.9169	pathogenic	-0.845	Destabilizing	0.999	D	0.824	deleterious	N	0.479254099	None	None	N
T/S	0.3867	ambiguous	0.3567	ambiguous	-1.376	Destabilizing	0.997	D	0.754	deleterious	N	0.478661259	None	None	N
T/V	0.4416	ambiguous	0.4049	ambiguous	-0.259	Destabilizing	0.998	D	0.816	deleterious	None	None	None	None	N
T/W	0.975	likely_pathogenic	0.9691	pathogenic	-0.592	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
T/Y	0.9251	likely_pathogenic	0.9125	pathogenic	-0.306	Destabilizing	1.0	D	0.864	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.