TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18848	56767;56768;56769	chr2:178599251;178599250;178599249	chr2:179463978;179463977;179463976
N2AB	17207	51844;51845;51846	chr2:178599251;178599250;178599249	chr2:179463978;179463977;179463976
N2A	16280	49063;49064;49065	chr2:178599251;178599250;178599249	chr2:179463978;179463977;179463976
N2B	9783	29572;29573;29574	chr2:178599251;178599250;178599249	chr2:179463978;179463977;179463976
Novex-1	9908	29947;29948;29949	chr2:178599251;178599250;178599249	chr2:179463978;179463977;179463976
Novex-2	9975	30148;30149;30150	chr2:178599251;178599250;178599249	chr2:179463978;179463977;179463976
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: Fn3-24
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.8482
• 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	rs2052641171	None	0.961	N	0.461	0.204	0.272639205421	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
K/E	rs2052641171	None	0.961	N	0.461	0.204	0.272639205421	gnomAD-4.0.0	6.57765E-06	None	None	None	None	N	None	0	6.55652E-05	None	0	0	None	0	0	0	0	0
K/R	rs879138127	None	0.031	N	0.139	0.084	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs879138127	None	0.031	N	0.139	0.084	None	gnomAD-4.0.0	6.57843E-06	None	None	None	None	N	None	2.41383E-05	0	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	0.5057	ambiguous	0.5748	pathogenic	0.086	Stabilizing	0.97	D	0.434	neutral	None	None	None	None	N
K/C	0.72	likely_pathogenic	0.7195	pathogenic	-0.301	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
K/D	0.6634	likely_pathogenic	0.7247	pathogenic	-0.218	Destabilizing	0.996	D	0.473	neutral	None	None	None	None	N
K/E	0.4179	ambiguous	0.4839	ambiguous	-0.213	Destabilizing	0.961	D	0.461	neutral	N	0.448616072	None	None	N
K/F	0.8803	likely_pathogenic	0.8967	pathogenic	-0.152	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
K/G	0.4271	ambiguous	0.4996	ambiguous	-0.084	Destabilizing	0.985	D	0.471	neutral	None	None	None	None	N
K/H	0.2961	likely_benign	0.3085	benign	-0.211	Destabilizing	0.999	D	0.499	neutral	None	None	None	None	N
K/I	0.7516	likely_pathogenic	0.7774	pathogenic	0.455	Stabilizing	0.998	D	0.607	neutral	N	0.498391531	None	None	N
K/L	0.5869	likely_pathogenic	0.6429	pathogenic	0.455	Stabilizing	0.97	D	0.471	neutral	None	None	None	None	N
K/M	0.4774	ambiguous	0.5267	ambiguous	0.016	Stabilizing	1.0	D	0.501	neutral	None	None	None	None	N
K/N	0.5045	ambiguous	0.5693	pathogenic	0.122	Stabilizing	0.994	D	0.455	neutral	N	0.379137344	None	None	N
K/P	0.853	likely_pathogenic	0.8865	pathogenic	0.357	Stabilizing	0.999	D	0.497	neutral	None	None	None	None	N
K/Q	0.1998	likely_benign	0.2274	benign	-0.005	Destabilizing	0.989	D	0.487	neutral	N	0.505336146	None	None	N
K/R	0.0797	likely_benign	0.0853	benign	-0.033	Destabilizing	0.031	N	0.139	neutral	N	0.398323324	None	None	N
K/S	0.5247	ambiguous	0.6074	pathogenic	-0.24	Destabilizing	0.985	D	0.454	neutral	None	None	None	None	N
K/T	0.3968	ambiguous	0.4709	ambiguous	-0.104	Destabilizing	0.98	D	0.465	neutral	N	0.491772203	None	None	N
K/V	0.6332	likely_pathogenic	0.6736	pathogenic	0.357	Stabilizing	0.996	D	0.491	neutral	None	None	None	None	N
K/W	0.8424	likely_pathogenic	0.8552	pathogenic	-0.25	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
K/Y	0.6985	likely_pathogenic	0.7114	pathogenic	0.102	Stabilizing	0.999	D	0.567	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.