TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27210	81853;81854;81855	chr2:178564504;178564503;178564502	chr2:179429231;179429230;179429229
N2AB	25569	76930;76931;76932	chr2:178564504;178564503;178564502	chr2:179429231;179429230;179429229
N2A	24642	74149;74150;74151	chr2:178564504;178564503;178564502	chr2:179429231;179429230;179429229
N2B	18145	54658;54659;54660	chr2:178564504;178564503;178564502	chr2:179429231;179429230;179429229
Novex-1	18270	55033;55034;55035	chr2:178564504;178564503;178564502	chr2:179429231;179429230;179429229
Novex-2	18337	55234;55235;55236	chr2:178564504;178564503;178564502	chr2:179429231;179429230;179429229
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: Fn3-86
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1465
• 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	0.892	N	0.431	0.236	0.28492961333	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
K/T	rs1241055435	-1.256	0.967	N	0.708	0.409	0.349429436713	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	2.93E-05	None	0	0	None	0	None	0	0	0
K/T	rs1241055435	-1.256	0.967	N	0.708	0.409	0.349429436713	gnomAD-4.0.0	1.59473E-06	None	None	None	None	N	None	0	2.29674E-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	0.9195	likely_pathogenic	0.8878	pathogenic	-1.37	Destabilizing	0.916	D	0.525	neutral	None	None	None	None	N
K/C	0.8107	likely_pathogenic	0.7727	pathogenic	-1.445	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
K/D	0.9916	likely_pathogenic	0.988	pathogenic	-1.447	Destabilizing	0.987	D	0.779	deleterious	None	None	None	None	N
K/E	0.8395	likely_pathogenic	0.7797	pathogenic	-1.2	Destabilizing	0.892	D	0.431	neutral	N	0.466190998	None	None	N
K/F	0.9831	likely_pathogenic	0.9745	pathogenic	-0.724	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
K/G	0.9568	likely_pathogenic	0.9384	pathogenic	-1.812	Destabilizing	0.975	D	0.716	prob.delet.	None	None	None	None	N
K/H	0.7447	likely_pathogenic	0.6908	pathogenic	-1.945	Destabilizing	0.997	D	0.785	deleterious	None	None	None	None	N
K/I	0.9177	likely_pathogenic	0.8799	pathogenic	-0.14	Destabilizing	0.983	D	0.845	deleterious	N	0.502452414	None	None	N
K/L	0.7695	likely_pathogenic	0.7376	pathogenic	-0.14	Destabilizing	0.975	D	0.716	prob.delet.	None	None	None	None	N
K/M	0.6349	likely_pathogenic	0.57	pathogenic	-0.474	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
K/N	0.9558	likely_pathogenic	0.9378	pathogenic	-1.499	Destabilizing	0.967	D	0.612	neutral	N	0.483031486	None	None	N
K/P	0.9987	likely_pathogenic	0.9981	pathogenic	-0.527	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
K/Q	0.4371	ambiguous	0.366	ambiguous	-1.291	Destabilizing	0.967	D	0.591	neutral	N	0.467316633	None	None	N
K/R	0.0736	likely_benign	0.0697	benign	-1.019	Destabilizing	0.025	N	0.19	neutral	N	0.410177901	None	None	N
K/S	0.9687	likely_pathogenic	0.9543	pathogenic	-2.084	Highly Destabilizing	0.916	D	0.495	neutral	None	None	None	None	N
K/T	0.8915	likely_pathogenic	0.8457	pathogenic	-1.6	Destabilizing	0.967	D	0.708	prob.delet.	N	0.48886761	None	None	N
K/V	0.8855	likely_pathogenic	0.8391	pathogenic	-0.527	Destabilizing	0.987	D	0.804	deleterious	None	None	None	None	N
K/W	0.9693	likely_pathogenic	0.9541	pathogenic	-0.724	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
K/Y	0.9375	likely_pathogenic	0.9168	pathogenic	-0.372	Destabilizing	0.996	D	0.836	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.