TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18078	54457;54458;54459	chr2:178604857;178604856;178604855	chr2:179469584;179469583;179469582
N2AB	16437	49534;49535;49536	chr2:178604857;178604856;178604855	chr2:179469584;179469583;179469582
N2A	15510	46753;46754;46755	chr2:178604857;178604856;178604855	chr2:179469584;179469583;179469582
N2B	9013	27262;27263;27264	chr2:178604857;178604856;178604855	chr2:179469584;179469583;179469582
Novex-1	9138	27637;27638;27639	chr2:178604857;178604856;178604855	chr2:179469584;179469583;179469582
Novex-2	9205	27838;27839;27840	chr2:178604857;178604856;178604855	chr2:179469584;179469583;179469582
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: Fn3-19
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.5628
• 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	0.989	N	0.467	0.328	0.317958651998	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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	0.8733	likely_pathogenic	0.8914	pathogenic	-0.352	Destabilizing	0.992	D	0.408	neutral	None	None	None	None	N
K/C	0.9313	likely_pathogenic	0.9341	pathogenic	-0.438	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
K/D	0.9504	likely_pathogenic	0.9565	pathogenic	-0.159	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	N
K/E	0.8011	likely_pathogenic	0.8247	pathogenic	-0.085	Destabilizing	0.989	D	0.467	neutral	N	0.499509039	None	None	N
K/F	0.9712	likely_pathogenic	0.9739	pathogenic	-0.216	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
K/G	0.8848	likely_pathogenic	0.8946	pathogenic	-0.686	Destabilizing	0.999	D	0.442	neutral	None	None	None	None	N
K/H	0.6091	likely_pathogenic	0.6158	pathogenic	-1.135	Destabilizing	1.0	D	0.461	neutral	None	None	None	None	N
K/I	0.9266	likely_pathogenic	0.9375	pathogenic	0.492	Stabilizing	0.994	D	0.64	neutral	N	0.515806643	None	None	N
K/L	0.818	likely_pathogenic	0.8246	pathogenic	0.492	Stabilizing	0.983	D	0.407	neutral	None	None	None	None	N
K/M	0.7158	likely_pathogenic	0.7325	pathogenic	0.457	Stabilizing	0.96	D	0.385	neutral	None	None	None	None	N
K/N	0.8946	likely_pathogenic	0.9036	pathogenic	-0.269	Destabilizing	0.998	D	0.441	neutral	N	0.457179627	None	None	N
K/P	0.9908	likely_pathogenic	0.9908	pathogenic	0.242	Stabilizing	1.0	D	0.487	neutral	None	None	None	None	N
K/Q	0.4419	ambiguous	0.4591	ambiguous	-0.435	Destabilizing	0.998	D	0.461	neutral	N	0.469706207	None	None	N
K/R	0.1135	likely_benign	0.1121	benign	-0.496	Destabilizing	0.733	D	0.287	neutral	N	0.451659164	None	None	N
K/S	0.8631	likely_pathogenic	0.8828	pathogenic	-0.884	Destabilizing	0.996	D	0.43	neutral	None	None	None	None	N
K/T	0.5356	ambiguous	0.5881	pathogenic	-0.62	Destabilizing	0.998	D	0.399	neutral	N	0.391991998	None	None	N
K/V	0.8643	likely_pathogenic	0.8843	pathogenic	0.242	Stabilizing	0.983	D	0.434	neutral	None	None	None	None	N
K/W	0.9583	likely_pathogenic	0.9612	pathogenic	-0.112	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
K/Y	0.932	likely_pathogenic	0.9365	pathogenic	0.216	Stabilizing	1.0	D	0.6	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.