TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14130	42613;42614;42615	chr2:178634393;178634392;178634391	chr2:179499120;179499119;179499118
N2AB	12489	37690;37691;37692	chr2:178634393;178634392;178634391	chr2:179499120;179499119;179499118
N2A	11562	34909;34910;34911	chr2:178634393;178634392;178634391	chr2:179499120;179499119;179499118
N2B	5065	15418;15419;15420	chr2:178634393;178634392;178634391	chr2:179499120;179499119;179499118
Novex-1	5190	15793;15794;15795	chr2:178634393;178634392;178634391	chr2:179499120;179499119;179499118
Novex-2	5257	15994;15995;15996	chr2:178634393;178634392;178634391	chr2:179499120;179499119;179499118
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-91
• Domain position: 77
• Structural Position: 163
• Q(SASA): 0.5443
• 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/N	None	None	0.92	N	0.519	0.153	0.139678290688	gnomAD-4.0.0	2.40078E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31258E-06	0	3.66327E-05

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	0.3606	ambiguous	0.427	ambiguous	-0.231	Destabilizing	0.759	D	0.385	neutral	None	None	None	None	N
K/C	0.7225	likely_pathogenic	0.7567	pathogenic	-0.365	Destabilizing	0.999	D	0.504	neutral	None	None	None	None	N
K/D	0.6601	likely_pathogenic	0.726	pathogenic	0.326	Stabilizing	0.884	D	0.58	neutral	None	None	None	None	N
K/E	0.1645	likely_benign	0.2093	benign	0.363	Stabilizing	0.134	N	0.174	neutral	N	0.440884478	None	None	N
K/F	0.7983	likely_pathogenic	0.8435	pathogenic	-0.301	Destabilizing	0.991	D	0.545	neutral	None	None	None	None	N
K/G	0.5232	ambiguous	0.6335	pathogenic	-0.48	Destabilizing	0.939	D	0.567	neutral	None	None	None	None	N
K/H	0.3636	ambiguous	0.3861	ambiguous	-0.758	Destabilizing	0.997	D	0.554	neutral	None	None	None	None	N
K/I	0.3339	likely_benign	0.3788	ambiguous	0.36	Stabilizing	0.884	D	0.571	neutral	None	None	None	None	N
K/L	0.4121	ambiguous	0.4657	ambiguous	0.36	Stabilizing	0.759	D	0.499	neutral	None	None	None	None	N
K/M	0.2112	likely_benign	0.2283	benign	0.2	Stabilizing	0.509	D	0.295	neutral	N	0.438149757	None	None	N
K/N	0.3926	ambiguous	0.4496	ambiguous	0.109	Stabilizing	0.92	D	0.519	neutral	N	0.447022625	None	None	N
K/P	0.8503	likely_pathogenic	0.9099	pathogenic	0.193	Stabilizing	0.969	D	0.588	neutral	None	None	None	None	N
K/Q	0.1215	likely_benign	0.1334	benign	-0.059	Destabilizing	0.92	D	0.551	neutral	N	0.453119563	None	None	N
K/R	0.0943	likely_benign	0.1048	benign	-0.115	Destabilizing	0.92	D	0.515	neutral	N	0.443671065	None	None	N
K/S	0.3821	ambiguous	0.4522	ambiguous	-0.53	Destabilizing	0.373	N	0.164	neutral	None	None	None	None	N
K/T	0.1315	likely_benign	0.1464	benign	-0.319	Destabilizing	0.061	N	0.233	neutral	N	0.426921516	None	None	N
K/V	0.3057	likely_benign	0.359	ambiguous	0.193	Stabilizing	0.884	D	0.571	neutral	None	None	None	None	N
K/W	0.827	likely_pathogenic	0.8603	pathogenic	-0.218	Destabilizing	0.999	D	0.511	neutral	None	None	None	None	N
K/Y	0.6758	likely_pathogenic	0.719	pathogenic	0.115	Stabilizing	0.997	D	0.541	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.