TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20958	63097;63098;63099	chr2:178588853;178588852;178588851	chr2:179453580;179453579;179453578
N2AB	19317	58174;58175;58176	chr2:178588853;178588852;178588851	chr2:179453580;179453579;179453578
N2A	18390	55393;55394;55395	chr2:178588853;178588852;178588851	chr2:179453580;179453579;179453578
N2B	11893	35902;35903;35904	chr2:178588853;178588852;178588851	chr2:179453580;179453579;179453578
Novex-1	12018	36277;36278;36279	chr2:178588853;178588852;178588851	chr2:179453580;179453579;179453578
Novex-2	12085	36478;36479;36480	chr2:178588853;178588852;178588851	chr2:179453580;179453579;179453578
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: Fn3-39
• Domain position: 95
• Structural Position: 131
• Q(SASA): 0.4785
• 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	0.991	N	0.488	0.176	0.258283824007	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/R	rs2049627530	None	0.451	N	0.297	0.116	0.168933306366	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
K/R	rs2049627530	None	0.451	N	0.297	0.116	0.168933306366	gnomAD-4.0.0	6.57635E-06	None	None	None	None	N	None	0	6.55394E-05	None	0	0	None	0	0	0	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	0.4304	ambiguous	0.3902	ambiguous	-0.264	Destabilizing	0.997	D	0.553	neutral	None	None	None	None	N
K/C	0.6054	likely_pathogenic	0.538	ambiguous	-0.377	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
K/D	0.8308	likely_pathogenic	0.8135	pathogenic	0.228	Stabilizing	0.999	D	0.695	prob.delet.	None	None	None	None	N
K/E	0.298	likely_benign	0.2829	benign	0.265	Stabilizing	0.991	D	0.488	neutral	N	0.469541451	None	None	N
K/F	0.8294	likely_pathogenic	0.7784	pathogenic	-0.344	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/G	0.5528	ambiguous	0.526	ambiguous	-0.525	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	N
K/H	0.3651	ambiguous	0.3182	benign	-0.912	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
K/I	0.4812	ambiguous	0.4297	ambiguous	0.359	Stabilizing	1.0	D	0.823	deleterious	N	0.471160839	None	None	N
K/L	0.5039	ambiguous	0.4488	ambiguous	0.359	Stabilizing	0.999	D	0.587	neutral	None	None	None	None	N
K/M	0.3292	likely_benign	0.2923	benign	0.288	Stabilizing	1.0	D	0.685	prob.delet.	None	None	None	None	N
K/N	0.6833	likely_pathogenic	0.6663	pathogenic	0.074	Stabilizing	0.999	D	0.611	neutral	N	0.490786032	None	None	N
K/P	0.9674	likely_pathogenic	0.9681	pathogenic	0.181	Stabilizing	1.0	D	0.691	prob.delet.	None	None	None	None	N
K/Q	0.1485	likely_benign	0.1381	benign	-0.131	Destabilizing	0.997	D	0.63	neutral	N	0.472666367	None	None	N
K/R	0.0787	likely_benign	0.0753	benign	-0.191	Destabilizing	0.451	N	0.297	neutral	N	0.45567533	None	None	N
K/S	0.5818	likely_pathogenic	0.5537	ambiguous	-0.573	Destabilizing	0.997	D	0.599	neutral	None	None	None	None	N
K/T	0.2473	likely_benign	0.2361	benign	-0.361	Destabilizing	0.999	D	0.648	neutral	N	0.496444517	None	None	N
K/V	0.3424	ambiguous	0.3036	benign	0.181	Stabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
K/W	0.8185	likely_pathogenic	0.7645	pathogenic	-0.236	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
K/Y	0.7491	likely_pathogenic	0.6894	pathogenic	0.1	Stabilizing	1.0	D	0.774	deleterious	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.