TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22833	68722;68723;68724	chr2:178578018;178578017;178578016	chr2:179442745;179442744;179442743
N2AB	21192	63799;63800;63801	chr2:178578018;178578017;178578016	chr2:179442745;179442744;179442743
N2A	20265	61018;61019;61020	chr2:178578018;178578017;178578016	chr2:179442745;179442744;179442743
N2B	13768	41527;41528;41529	chr2:178578018;178578017;178578016	chr2:179442745;179442744;179442743
Novex-1	13893	41902;41903;41904	chr2:178578018;178578017;178578016	chr2:179442745;179442744;179442743
Novex-2	13960	42103;42104;42105	chr2:178578018;178578017;178578016	chr2:179442745;179442744;179442743
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-53
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.6564
• Predicted PPI site: I

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
S/L	rs876658077	None	0.666	N	0.55	0.432	0.43656330218	gnomAD-4.0.0	1.59274E-06	None	None	None	None	I	None	5.66765E-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
S/A	0.2372	likely_benign	0.2193	benign	-0.633	Destabilizing	0.451	N	0.467	neutral	N	0.489429679	None	None	I
S/C	0.2002	likely_benign	0.1767	benign	-0.477	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	I
S/D	0.9761	likely_pathogenic	0.9744	pathogenic	-1.046	Destabilizing	0.841	D	0.401	neutral	None	None	None	None	I
S/E	0.9882	likely_pathogenic	0.9868	pathogenic	-0.891	Destabilizing	0.841	D	0.367	neutral	None	None	None	None	I
S/F	0.9565	likely_pathogenic	0.9485	pathogenic	-0.329	Destabilizing	0.974	D	0.758	deleterious	None	None	None	None	I
S/G	0.2557	likely_benign	0.253	benign	-1.029	Destabilizing	0.841	D	0.417	neutral	None	None	None	None	I
S/H	0.9719	likely_pathogenic	0.9704	pathogenic	-1.441	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	I
S/I	0.8607	likely_pathogenic	0.8367	pathogenic	0.361	Stabilizing	0.949	D	0.536	neutral	None	None	None	None	I
S/K	0.9968	likely_pathogenic	0.9965	pathogenic	-0.575	Destabilizing	0.841	D	0.394	neutral	None	None	None	None	I
S/L	0.5468	ambiguous	0.5038	ambiguous	0.361	Stabilizing	0.666	D	0.55	neutral	N	0.508228269	None	None	I
S/M	0.6857	likely_pathogenic	0.6409	pathogenic	0.296	Stabilizing	0.998	D	0.586	neutral	None	None	None	None	I
S/N	0.8592	likely_pathogenic	0.8559	pathogenic	-1.046	Destabilizing	0.841	D	0.451	neutral	None	None	None	None	I
S/P	0.9747	likely_pathogenic	0.9706	pathogenic	0.067	Stabilizing	0.966	D	0.531	neutral	N	0.505029173	None	None	I
S/Q	0.9816	likely_pathogenic	0.9794	pathogenic	-0.832	Destabilizing	0.974	D	0.503	neutral	None	None	None	None	I
S/R	0.9938	likely_pathogenic	0.9933	pathogenic	-0.882	Destabilizing	0.974	D	0.544	neutral	None	None	None	None	I
S/T	0.1064	likely_benign	0.096	benign	-0.769	Destabilizing	0.007	N	0.152	neutral	N	0.487038387	None	None	I
S/V	0.687	likely_pathogenic	0.6368	pathogenic	0.067	Stabilizing	0.725	D	0.52	neutral	None	None	None	None	I
S/W	0.9777	likely_pathogenic	0.9778	pathogenic	-0.577	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	I
S/Y	0.9601	likely_pathogenic	0.958	pathogenic	-0.171	Destabilizing	0.991	D	0.769	deleterious	None	None	None	None	I

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.