TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18943	57052;57053;57054	chr2:178598883;178598882;178598881	chr2:179463610;179463609;179463608
N2AB	17302	52129;52130;52131	chr2:178598883;178598882;178598881	chr2:179463610;179463609;179463608
N2A	16375	49348;49349;49350	chr2:178598883;178598882;178598881	chr2:179463610;179463609;179463608
N2B	9878	29857;29858;29859	chr2:178598883;178598882;178598881	chr2:179463610;179463609;179463608
Novex-1	10003	30232;30233;30234	chr2:178598883;178598882;178598881	chr2:179463610;179463609;179463608
Novex-2	10070	30433;30434;30435	chr2:178598883;178598882;178598881	chr2:179463610;179463609;179463608
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-25
• Domain position: 60
• Structural Position: 86
• Q(SASA): 0.2714
• 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/A	None	None	0.005	N	0.133	0.115	0.112648838833	gnomAD-4.0.0	1.5923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85992E-06	0	0
T/N	None	None	0.966	N	0.459	0.264	0.352048277211	gnomAD-4.0.0	4.77683E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57976E-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	0.0849	likely_benign	0.0823	benign	-0.153	Destabilizing	0.005	N	0.133	neutral	N	0.492790923	None	None	N
T/C	0.4818	ambiguous	0.4802	ambiguous	-0.544	Destabilizing	0.998	D	0.423	neutral	None	None	None	None	N
T/D	0.4573	ambiguous	0.4178	ambiguous	-0.193	Destabilizing	0.915	D	0.411	neutral	None	None	None	None	N
T/E	0.3805	ambiguous	0.3476	ambiguous	-0.283	Destabilizing	0.842	D	0.418	neutral	None	None	None	None	N
T/F	0.385	ambiguous	0.3508	ambiguous	-0.852	Destabilizing	0.974	D	0.495	neutral	None	None	None	None	N
T/G	0.2425	likely_benign	0.1874	benign	-0.18	Destabilizing	0.728	D	0.432	neutral	None	None	None	None	N
T/H	0.2973	likely_benign	0.2675	benign	-0.233	Destabilizing	0.998	D	0.49	neutral	None	None	None	None	N
T/I	0.2744	likely_benign	0.2471	benign	-0.196	Destabilizing	0.934	D	0.454	neutral	N	0.477322826	None	None	N
T/K	0.3013	likely_benign	0.2868	benign	-0.375	Destabilizing	0.842	D	0.423	neutral	None	None	None	None	N
T/L	0.1305	likely_benign	0.1194	benign	-0.196	Destabilizing	0.842	D	0.396	neutral	None	None	None	None	N
T/M	0.1161	likely_benign	0.12	benign	-0.351	Destabilizing	0.998	D	0.433	neutral	None	None	None	None	N
T/N	0.1362	likely_benign	0.1189	benign	-0.203	Destabilizing	0.966	D	0.459	neutral	N	0.463300481	None	None	N
T/P	0.0647	likely_benign	0.0632	benign	-0.161	Destabilizing	0.002	N	0.202	neutral	N	0.447693352	None	None	N
T/Q	0.2474	likely_benign	0.2225	benign	-0.387	Destabilizing	0.974	D	0.467	neutral	None	None	None	None	N
T/R	0.2888	likely_benign	0.2865	benign	-0.067	Destabilizing	0.974	D	0.453	neutral	None	None	None	None	N
T/S	0.1293	likely_benign	0.1125	benign	-0.349	Destabilizing	0.454	N	0.463	neutral	N	0.489097257	None	None	N
T/V	0.188	likely_benign	0.1705	benign	-0.161	Destabilizing	0.728	D	0.419	neutral	None	None	None	None	N
T/W	0.7297	likely_pathogenic	0.7116	pathogenic	-0.972	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	N
T/Y	0.4051	ambiguous	0.3619	ambiguous	-0.648	Destabilizing	0.991	D	0.497	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.