TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15416	46471;46472;46473	chr2:178620275;178620274;178620273	chr2:179485002;179485001;179485000
N2AB	13775	41548;41549;41550	chr2:178620275;178620274;178620273	chr2:179485002;179485001;179485000
N2A	12848	38767;38768;38769	chr2:178620275;178620274;178620273	chr2:179485002;179485001;179485000
N2B	6351	19276;19277;19278	chr2:178620275;178620274;178620273	chr2:179485002;179485001;179485000
Novex-1	6476	19651;19652;19653	chr2:178620275;178620274;178620273	chr2:179485002;179485001;179485000
Novex-2	6543	19852;19853;19854	chr2:178620275;178620274;178620273	chr2:179485002;179485001;179485000
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-106
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.5311
• 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
R/T	None	None	0.801	N	0.377	0.317	0.609094465904	gnomAD-4.0.0	2.15149E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.77486E-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
R/A	0.5302	ambiguous	0.7525	pathogenic	-0.131	Destabilizing	0.688	D	0.369	neutral	None	None	None	None	N
R/C	0.4517	ambiguous	0.6109	pathogenic	-0.229	Destabilizing	0.998	D	0.375	neutral	None	None	None	None	N
R/D	0.8073	likely_pathogenic	0.9149	pathogenic	0.074	Stabilizing	0.842	D	0.396	neutral	None	None	None	None	N
R/E	0.4989	ambiguous	0.6663	pathogenic	0.14	Stabilizing	0.525	D	0.387	neutral	None	None	None	None	N
R/F	0.8158	likely_pathogenic	0.9053	pathogenic	-0.349	Destabilizing	0.991	D	0.407	neutral	None	None	None	None	N
R/G	0.3429	ambiguous	0.5716	pathogenic	-0.333	Destabilizing	0.801	D	0.337	neutral	N	0.426029143	None	None	N
R/H	0.2302	likely_benign	0.3166	benign	-0.762	Destabilizing	0.991	D	0.375	neutral	None	None	None	None	N
R/I	0.5108	ambiguous	0.6507	pathogenic	0.368	Stabilizing	0.966	D	0.431	neutral	N	0.509480767	None	None	N
R/K	0.0887	likely_benign	0.1295	benign	-0.097	Destabilizing	0.002	N	0.105	neutral	N	0.367671264	None	None	N
R/L	0.4331	ambiguous	0.5746	pathogenic	0.368	Stabilizing	0.842	D	0.337	neutral	None	None	None	None	N
R/M	0.4535	ambiguous	0.6307	pathogenic	0.003	Stabilizing	0.991	D	0.401	neutral	None	None	None	None	N
R/N	0.7029	likely_pathogenic	0.8688	pathogenic	0.195	Stabilizing	0.842	D	0.333	neutral	None	None	None	None	N
R/P	0.8294	likely_pathogenic	0.9053	pathogenic	0.222	Stabilizing	0.915	D	0.419	neutral	None	None	None	None	N
R/Q	0.1639	likely_benign	0.2385	benign	0.05	Stabilizing	0.842	D	0.371	neutral	None	None	None	None	N
R/S	0.641	likely_pathogenic	0.8311	pathogenic	-0.279	Destabilizing	0.625	D	0.341	neutral	N	0.465491695	None	None	N
R/T	0.3991	ambiguous	0.6081	pathogenic	-0.072	Destabilizing	0.801	D	0.377	neutral	N	0.499318899	None	None	N
R/V	0.5694	likely_pathogenic	0.7183	pathogenic	0.222	Stabilizing	0.915	D	0.459	neutral	None	None	None	None	N
R/W	0.4492	ambiguous	0.5561	ambiguous	-0.337	Destabilizing	0.998	D	0.425	neutral	None	None	None	None	N
R/Y	0.7253	likely_pathogenic	0.8499	pathogenic	0.07	Stabilizing	0.991	D	0.392	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.