TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22385	67378;67379;67380	chr2:178580134;178580133;178580132	chr2:179444861;179444860;179444859
N2AB	20744	62455;62456;62457	chr2:178580134;178580133;178580132	chr2:179444861;179444860;179444859
N2A	19817	59674;59675;59676	chr2:178580134;178580133;178580132	chr2:179444861;179444860;179444859
N2B	13320	40183;40184;40185	chr2:178580134;178580133;178580132	chr2:179444861;179444860;179444859
Novex-1	13445	40558;40559;40560	chr2:178580134;178580133;178580132	chr2:179444861;179444860;179444859
Novex-2	13512	40759;40760;40761	chr2:178580134;178580133;178580132	chr2:179444861;179444860;179444859
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-50
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6919
• 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
P/S	rs781562260	-0.181	0.988	N	0.604	0.433	0.343560092441	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
P/S	rs781562260	-0.181	0.988	N	0.604	0.433	0.343560092441	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
P/S	rs781562260	-0.181	0.988	N	0.604	0.433	0.343560092441	gnomAD-4.0.0	9.29885E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.18696E-05	0	1.60169E-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
P/A	0.1182	likely_benign	0.1206	benign	-0.736	Destabilizing	0.958	D	0.549	neutral	N	0.518174944	None	None	I
P/C	0.7024	likely_pathogenic	0.7141	pathogenic	-0.665	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
P/D	0.5778	likely_pathogenic	0.6652	pathogenic	-0.467	Destabilizing	0.995	D	0.683	prob.neutral	None	None	None	None	I
P/E	0.3507	ambiguous	0.4216	ambiguous	-0.572	Destabilizing	0.991	D	0.617	neutral	None	None	None	None	I
P/F	0.8011	likely_pathogenic	0.8196	pathogenic	-0.867	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	I
P/G	0.4712	ambiguous	0.4964	ambiguous	-0.902	Destabilizing	0.991	D	0.607	neutral	None	None	None	None	I
P/H	0.3035	likely_benign	0.3386	benign	-0.422	Destabilizing	0.998	D	0.609	neutral	N	0.4890851	None	None	I
P/I	0.5162	ambiguous	0.5294	ambiguous	-0.442	Destabilizing	0.995	D	0.655	neutral	None	None	None	None	I
P/K	0.3229	likely_benign	0.3814	ambiguous	-0.599	Destabilizing	0.938	D	0.601	neutral	None	None	None	None	I
P/L	0.2626	likely_benign	0.2588	benign	-0.442	Destabilizing	0.988	D	0.659	neutral	N	0.491985163	None	None	I
P/M	0.4891	ambiguous	0.4804	ambiguous	-0.345	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	I
P/N	0.4054	ambiguous	0.4227	ambiguous	-0.33	Destabilizing	0.991	D	0.666	neutral	None	None	None	None	I
P/Q	0.2033	likely_benign	0.2168	benign	-0.598	Destabilizing	0.991	D	0.657	neutral	None	None	None	None	I
P/R	0.2329	likely_benign	0.2859	benign	-0.022	Destabilizing	0.142	N	0.507	neutral	N	0.515540071	None	None	I
P/S	0.1939	likely_benign	0.2002	benign	-0.732	Destabilizing	0.988	D	0.604	neutral	N	0.49604686	None	None	I
P/T	0.1756	likely_benign	0.1864	benign	-0.735	Destabilizing	0.988	D	0.638	neutral	N	0.486589885	None	None	I
P/V	0.3185	likely_benign	0.33	benign	-0.504	Destabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	I
P/W	0.8797	likely_pathogenic	0.9137	pathogenic	-0.933	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/Y	0.7047	likely_pathogenic	0.7446	pathogenic	-0.646	Destabilizing	1.0	D	0.618	neutral	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.