TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4932	15019;15020;15021	chr2:178735652;178735651;178735650	chr2:179600379;179600378;179600377
N2AB	4615	14068;14069;14070	chr2:178735652;178735651;178735650	chr2:179600379;179600378;179600377
N2A	3688	11287;11288;11289	chr2:178735652;178735651;178735650	chr2:179600379;179600378;179600377
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-32
• Domain position: 45
• Structural Position: 111
• Q(SASA): 0.8977
• 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
K/R	None	None	0.035	N	0.208	0.076	0.166414681773	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
K/A	0.3942	ambiguous	0.5527	ambiguous	-0.107	Destabilizing	0.863	D	0.364	neutral	None	None	None	None	N
K/C	0.7589	likely_pathogenic	0.8459	pathogenic	-0.624	Destabilizing	0.999	D	0.367	neutral	None	None	None	None	N
K/D	0.5362	ambiguous	0.7257	pathogenic	-0.395	Destabilizing	0.969	D	0.415	neutral	None	None	None	None	N
K/E	0.2203	likely_benign	0.3558	ambiguous	-0.42	Destabilizing	0.92	D	0.306	neutral	N	0.412698534	None	None	N
K/F	0.762	likely_pathogenic	0.867	pathogenic	-0.513	Destabilizing	0.982	D	0.382	neutral	None	None	None	None	N
K/G	0.3931	ambiguous	0.5367	ambiguous	-0.188	Destabilizing	0.969	D	0.413	neutral	None	None	None	None	N
K/H	0.3812	ambiguous	0.4986	ambiguous	-0.238	Destabilizing	0.997	D	0.369	neutral	None	None	None	None	N
K/I	0.4192	ambiguous	0.5728	pathogenic	0.028	Stabilizing	0.953	D	0.396	neutral	N	0.452884811	None	None	N
K/L	0.4224	ambiguous	0.5675	pathogenic	0.028	Stabilizing	0.759	D	0.345	neutral	None	None	None	None	N
K/M	0.2887	likely_benign	0.4024	ambiguous	-0.27	Destabilizing	0.373	N	0.272	neutral	None	None	None	None	N
K/N	0.4026	ambiguous	0.5638	ambiguous	-0.175	Destabilizing	0.959	D	0.341	neutral	N	0.442821883	None	None	N
K/P	0.5156	ambiguous	0.6509	pathogenic	0.002	Stabilizing	0.046	N	0.267	neutral	None	None	None	None	N
K/Q	0.1802	likely_benign	0.2475	benign	-0.305	Destabilizing	0.92	D	0.327	neutral	N	0.439111238	None	None	N
K/R	0.0819	likely_benign	0.0871	benign	-0.249	Destabilizing	0.035	N	0.208	neutral	N	0.424991264	None	None	N
K/S	0.4097	ambiguous	0.5746	pathogenic	-0.518	Destabilizing	0.969	D	0.308	neutral	None	None	None	None	N
K/T	0.2616	likely_benign	0.3949	ambiguous	-0.446	Destabilizing	0.959	D	0.385	neutral	N	0.44689936	None	None	N
K/V	0.403	ambiguous	0.5565	ambiguous	0.002	Stabilizing	0.884	D	0.417	neutral	None	None	None	None	N
K/W	0.6909	likely_pathogenic	0.7858	pathogenic	-0.629	Destabilizing	0.999	D	0.393	neutral	None	None	None	None	N
K/Y	0.6113	likely_pathogenic	0.7395	pathogenic	-0.296	Destabilizing	0.997	D	0.379	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.