TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21401	64426;64427;64428	chr2:178586700;178586699;178586698	chr2:179451427;179451426;179451425
N2AB	19760	59503;59504;59505	chr2:178586700;178586699;178586698	chr2:179451427;179451426;179451425
N2A	18833	56722;56723;56724	chr2:178586700;178586699;178586698	chr2:179451427;179451426;179451425
N2B	12336	37231;37232;37233	chr2:178586700;178586699;178586698	chr2:179451427;179451426;179451425
Novex-1	12461	37606;37607;37608	chr2:178586700;178586699;178586698	chr2:179451427;179451426;179451425
Novex-2	12528	37807;37808;37809	chr2:178586700;178586699;178586698	chr2:179451427;179451426;179451425
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-43
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1062
• 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
Y/C	None	None	1.0	D	0.864	0.794	None	gnomAD-4.0.0	1.59274E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8612E-06	0	0
Y/H	None	None	1.0	D	0.806	0.819	0.743204782601	gnomAD-4.0.0	1.59272E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86121E-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
Y/A	0.9984	likely_pathogenic	0.9982	pathogenic	-3.437	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/C	0.9741	likely_pathogenic	0.9697	pathogenic	-1.964	Destabilizing	1.0	D	0.864	deleterious	D	0.635171675	None	None	N
Y/D	0.9966	likely_pathogenic	0.9964	pathogenic	-3.961	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.651625004	None	None	N
Y/E	0.9991	likely_pathogenic	0.9991	pathogenic	-3.748	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/F	0.2669	likely_benign	0.2661	benign	-1.386	Destabilizing	0.999	D	0.651	neutral	D	0.551644197	None	None	N
Y/G	0.9935	likely_pathogenic	0.993	pathogenic	-3.837	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
Y/H	0.9882	likely_pathogenic	0.9863	pathogenic	-2.571	Highly Destabilizing	1.0	D	0.806	deleterious	D	0.634768066	None	None	N
Y/I	0.9829	likely_pathogenic	0.9789	pathogenic	-2.075	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/K	0.9988	likely_pathogenic	0.9987	pathogenic	-2.585	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/L	0.9709	likely_pathogenic	0.9662	pathogenic	-2.075	Highly Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
Y/M	0.9926	likely_pathogenic	0.991	pathogenic	-1.778	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
Y/N	0.9838	likely_pathogenic	0.9807	pathogenic	-3.418	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.6514232	None	None	N
Y/P	0.9996	likely_pathogenic	0.9994	pathogenic	-2.548	Highly Destabilizing	1.0	D	0.934	deleterious	None	None	None	None	N
Y/Q	0.999	likely_pathogenic	0.9989	pathogenic	-3.148	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/R	0.9955	likely_pathogenic	0.9952	pathogenic	-2.355	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/S	0.9934	likely_pathogenic	0.9926	pathogenic	-3.681	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.6514232	None	None	N
Y/T	0.998	likely_pathogenic	0.9976	pathogenic	-3.352	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/V	0.9747	likely_pathogenic	0.9702	pathogenic	-2.548	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
Y/W	0.8802	likely_pathogenic	0.8711	pathogenic	-0.679	Destabilizing	1.0	D	0.79	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.