TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33488	100687;100688;100689	chr2:178536285;178536284;178536283	chr2:179401012;179401011;179401010
N2AB	31847	95764;95765;95766	chr2:178536285;178536284;178536283	chr2:179401012;179401011;179401010
N2A	30920	92983;92984;92985	chr2:178536285;178536284;178536283	chr2:179401012;179401011;179401010
N2B	24423	73492;73493;73494	chr2:178536285;178536284;178536283	chr2:179401012;179401011;179401010
Novex-1	24548	73867;73868;73869	chr2:178536285;178536284;178536283	chr2:179401012;179401011;179401010
Novex-2	24615	74068;74069;74070	chr2:178536285;178536284;178536283	chr2:179401012;179401011;179401010
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: Fn3-131
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.615
• 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/R	rs1415630189	None	0.003	N	0.305	0.089	0.222439326576	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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	0.3481	ambiguous	0.3417	ambiguous	-0.152	Destabilizing	0.359	N	0.513	neutral	None	None	None	None	N
K/C	0.695	likely_pathogenic	0.6436	pathogenic	-0.25	Destabilizing	0.989	D	0.853	deleterious	None	None	None	None	N
K/D	0.7451	likely_pathogenic	0.7774	pathogenic	0.089	Stabilizing	0.797	D	0.432	neutral	None	None	None	None	N
K/E	0.2618	likely_benign	0.2639	benign	0.135	Stabilizing	0.297	N	0.487	neutral	N	0.495463082	None	None	N
K/F	0.7925	likely_pathogenic	0.78	pathogenic	-0.121	Destabilizing	0.989	D	0.785	deleterious	None	None	None	None	N
K/G	0.5287	ambiguous	0.5427	ambiguous	-0.437	Destabilizing	0.528	D	0.479	neutral	None	None	None	None	N
K/H	0.4051	ambiguous	0.3816	ambiguous	-0.815	Destabilizing	0.937	D	0.497	neutral	None	None	None	None	N
K/I	0.3204	likely_benign	0.322	benign	0.54	Stabilizing	0.857	D	0.838	deleterious	N	0.465680338	None	None	N
K/L	0.3975	ambiguous	0.3827	ambiguous	0.54	Stabilizing	0.528	D	0.479	neutral	None	None	None	None	N
K/M	0.3121	likely_benign	0.3009	benign	0.373	Stabilizing	0.968	D	0.495	neutral	None	None	None	None	N
K/N	0.5472	ambiguous	0.5794	pathogenic	0.025	Stabilizing	0.747	D	0.472	neutral	N	0.514379704	None	None	N
K/P	0.8702	likely_pathogenic	0.8898	pathogenic	0.34	Stabilizing	0.888	D	0.531	neutral	None	None	None	None	N
K/Q	0.1484	likely_benign	0.1382	benign	-0.121	Destabilizing	0.006	N	0.255	neutral	N	0.485595592	None	None	N
K/R	0.0932	likely_benign	0.0893	benign	-0.298	Destabilizing	0.003	N	0.305	neutral	N	0.484230155	None	None	N
K/S	0.4761	ambiguous	0.4845	ambiguous	-0.538	Destabilizing	0.359	N	0.54	neutral	None	None	None	None	N
K/T	0.2068	likely_benign	0.2051	benign	-0.315	Destabilizing	0.747	D	0.431	neutral	N	0.483784592	None	None	N
K/V	0.2819	likely_benign	0.2681	benign	0.34	Stabilizing	0.797	D	0.652	prob.neutral	None	None	None	None	N
K/W	0.883	likely_pathogenic	0.8761	pathogenic	-0.062	Destabilizing	0.989	D	0.845	deleterious	None	None	None	None	N
K/Y	0.7433	likely_pathogenic	0.7369	pathogenic	0.258	Stabilizing	0.888	D	0.813	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.