TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14323	43192;43193;43194	chr2:178633306;178633305;178633304	chr2:179498033;179498032;179498031
N2AB	12682	38269;38270;38271	chr2:178633306;178633305;178633304	chr2:179498033;179498032;179498031
N2A	11755	35488;35489;35490	chr2:178633306;178633305;178633304	chr2:179498033;179498032;179498031
N2B	5258	15997;15998;15999	chr2:178633306;178633305;178633304	chr2:179498033;179498032;179498031
Novex-1	5383	16372;16373;16374	chr2:178633306;178633305;178633304	chr2:179498033;179498032;179498031
Novex-2	5450	16573;16574;16575	chr2:178633306;178633305;178633304	chr2:179498033;179498032;179498031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-94
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.3095
• 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/E	None	None	0.435	N	0.411	0.168	0.149567049428	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
K/N	None	None	0.651	N	0.305	0.101	0.115124310173	gnomAD-4.0.0	1.59326E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43728E-05	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	0.743	likely_pathogenic	0.7555	pathogenic	-0.367	Destabilizing	0.505	D	0.318	neutral	None	None	None	None	N
K/C	0.8948	likely_pathogenic	0.9012	pathogenic	-0.471	Destabilizing	0.995	D	0.578	neutral	None	None	None	None	N
K/D	0.881	likely_pathogenic	0.8823	pathogenic	-0.079	Destabilizing	0.834	D	0.435	neutral	None	None	None	None	N
K/E	0.4391	ambiguous	0.4436	ambiguous	0.032	Stabilizing	0.435	N	0.411	neutral	N	0.432299766	None	None	N
K/F	0.9288	likely_pathogenic	0.9289	pathogenic	0.036	Stabilizing	0.982	D	0.554	neutral	None	None	None	None	N
K/G	0.8058	likely_pathogenic	0.8254	pathogenic	-0.728	Destabilizing	0.834	D	0.38	neutral	None	None	None	None	N
K/H	0.4728	ambiguous	0.5094	ambiguous	-0.961	Destabilizing	0.946	D	0.38	neutral	None	None	None	None	N
K/I	0.6589	likely_pathogenic	0.6156	pathogenic	0.562	Stabilizing	0.946	D	0.614	neutral	None	None	None	None	N
K/L	0.6576	likely_pathogenic	0.6438	pathogenic	0.562	Stabilizing	0.712	D	0.38	neutral	None	None	None	None	N
K/M	0.4865	ambiguous	0.4756	ambiguous	0.236	Stabilizing	0.976	D	0.374	neutral	N	0.487296835	None	None	N
K/N	0.6316	likely_pathogenic	0.6222	pathogenic	-0.386	Destabilizing	0.651	D	0.305	neutral	N	0.424244526	None	None	N
K/P	0.9793	likely_pathogenic	0.9826	pathogenic	0.283	Stabilizing	0.982	D	0.448	neutral	None	None	None	None	N
K/Q	0.2755	likely_benign	0.2819	benign	-0.402	Destabilizing	0.651	D	0.413	neutral	N	0.434517481	None	None	N
K/R	0.1024	likely_benign	0.1139	benign	-0.564	Destabilizing	0.001	N	0.079	neutral	N	0.371798799	None	None	N
K/S	0.7651	likely_pathogenic	0.77	pathogenic	-0.957	Destabilizing	0.712	D	0.313	neutral	None	None	None	None	N
K/T	0.4588	ambiguous	0.4325	ambiguous	-0.647	Destabilizing	0.791	D	0.32	neutral	N	0.431647687	None	None	N
K/V	0.6615	likely_pathogenic	0.6158	pathogenic	0.283	Stabilizing	0.946	D	0.469	neutral	None	None	None	None	N
K/W	0.9168	likely_pathogenic	0.9355	pathogenic	0.108	Stabilizing	0.995	D	0.596	neutral	None	None	None	None	N
K/Y	0.8	likely_pathogenic	0.8162	pathogenic	0.373	Stabilizing	0.982	D	0.504	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.