TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21029	63310;63311;63312	chr2:178588640;178588639;178588638	chr2:179453367;179453366;179453365
N2AB	19388	58387;58388;58389	chr2:178588640;178588639;178588638	chr2:179453367;179453366;179453365
N2A	18461	55606;55607;55608	chr2:178588640;178588639;178588638	chr2:179453367;179453366;179453365
N2B	11964	36115;36116;36117	chr2:178588640;178588639;178588638	chr2:179453367;179453366;179453365
Novex-1	12089	36490;36491;36492	chr2:178588640;178588639;178588638	chr2:179453367;179453366;179453365
Novex-2	12156	36691;36692;36693	chr2:178588640;178588639;178588638	chr2:179453367;179453366;179453365
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-40
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.6129
• 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
L/F	None	None	0.001	N	0.06	0.087	0.246773566709	gnomAD-4.0.0	1.60851E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88058E-06	0	0
L/P	None	None	0.912	N	0.399	0.282	0.71646297227	gnomAD-4.0.0	1.37496E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80349E-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
L/A	0.3548	ambiguous	0.2649	benign	-1.75	Destabilizing	0.207	N	0.334	neutral	None	None	None	None	N
L/C	0.5993	likely_pathogenic	0.51	ambiguous	-0.807	Destabilizing	0.981	D	0.32	neutral	None	None	None	None	N
L/D	0.8381	likely_pathogenic	0.7149	pathogenic	-1.361	Destabilizing	0.818	D	0.396	neutral	None	None	None	None	N
L/E	0.5486	ambiguous	0.4258	ambiguous	-1.333	Destabilizing	0.818	D	0.407	neutral	None	None	None	None	N
L/F	0.1575	likely_benign	0.1271	benign	-1.215	Destabilizing	0.001	N	0.06	neutral	N	0.492892498	None	None	N
L/G	0.6872	likely_pathogenic	0.5503	ambiguous	-2.087	Highly Destabilizing	0.563	D	0.385	neutral	None	None	None	None	N
L/H	0.2938	likely_benign	0.2271	benign	-1.232	Destabilizing	0.975	D	0.364	neutral	N	0.467226049	None	None	N
L/I	0.0794	likely_benign	0.0811	benign	-0.879	Destabilizing	0.001	N	0.068	neutral	N	0.393787083	None	None	N
L/K	0.3928	ambiguous	0.3165	benign	-1.197	Destabilizing	0.818	D	0.389	neutral	None	None	None	None	N
L/M	0.1228	likely_benign	0.114	benign	-0.6	Destabilizing	0.69	D	0.335	neutral	None	None	None	None	N
L/N	0.4521	ambiguous	0.3239	benign	-1.018	Destabilizing	0.818	D	0.41	neutral	None	None	None	None	N
L/P	0.6808	likely_pathogenic	0.5091	ambiguous	-1.141	Destabilizing	0.912	D	0.399	neutral	N	0.489582834	None	None	N
L/Q	0.2114	likely_benign	0.1634	benign	-1.175	Destabilizing	0.932	D	0.368	neutral	None	None	None	None	N
L/R	0.3184	likely_benign	0.2571	benign	-0.577	Destabilizing	0.773	D	0.381	neutral	N	0.453312602	None	None	N
L/S	0.3864	ambiguous	0.2758	benign	-1.581	Destabilizing	0.241	N	0.361	neutral	None	None	None	None	N
L/T	0.3064	likely_benign	0.2315	benign	-1.439	Destabilizing	0.008	N	0.119	neutral	None	None	None	None	N
L/V	0.1113	likely_benign	0.0989	benign	-1.141	Destabilizing	0.015	N	0.188	neutral	N	0.44938965	None	None	N
L/W	0.3448	ambiguous	0.2787	benign	-1.327	Destabilizing	0.944	D	0.359	neutral	None	None	None	None	N
L/Y	0.3696	ambiguous	0.2855	benign	-1.106	Destabilizing	0.241	N	0.367	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.