TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21735	65428;65429;65430	chr2:178584348;178584347;178584346	chr2:179449075;179449074;179449073
N2AB	20094	60505;60506;60507	chr2:178584348;178584347;178584346	chr2:179449075;179449074;179449073
N2A	19167	57724;57725;57726	chr2:178584348;178584347;178584346	chr2:179449075;179449074;179449073
N2B	12670	38233;38234;38235	chr2:178584348;178584347;178584346	chr2:179449075;179449074;179449073
Novex-1	12795	38608;38609;38610	chr2:178584348;178584347;178584346	chr2:179449075;179449074;179449073
Novex-2	12862	38809;38810;38811	chr2:178584348;178584347;178584346	chr2:179449075;179449074;179449073
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-45
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1716
• 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	rs1430331721	-1.715	0.997	N	0.674	0.376	0.542187413537	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	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	0.5012	ambiguous	0.4019	ambiguous	-3.326	Highly Destabilizing	0.525	D	0.594	neutral	None	None	None	None	N
Y/C	0.1297	likely_benign	0.1081	benign	-1.724	Destabilizing	0.997	D	0.674	neutral	N	0.434902987	None	None	N
Y/D	0.7612	likely_pathogenic	0.6644	pathogenic	-2.865	Highly Destabilizing	0.801	D	0.623	neutral	D	0.522020539	None	None	N
Y/E	0.8564	likely_pathogenic	0.7858	pathogenic	-2.734	Highly Destabilizing	0.842	D	0.621	neutral	None	None	None	None	N
Y/F	0.0975	likely_benign	0.0919	benign	-1.383	Destabilizing	0.891	D	0.657	neutral	N	0.430611888	None	None	N
Y/G	0.6398	likely_pathogenic	0.5318	ambiguous	-3.675	Highly Destabilizing	0.728	D	0.638	neutral	None	None	None	None	N
Y/H	0.1938	likely_benign	0.1507	benign	-1.93	Destabilizing	0.989	D	0.661	neutral	D	0.522020539	None	None	N
Y/I	0.4086	ambiguous	0.3744	ambiguous	-2.189	Highly Destabilizing	0.067	N	0.433	neutral	None	None	None	None	N
Y/K	0.7371	likely_pathogenic	0.6329	pathogenic	-1.987	Destabilizing	0.842	D	0.619	neutral	None	None	None	None	N
Y/L	0.465	ambiguous	0.4011	ambiguous	-2.189	Highly Destabilizing	0.525	D	0.601	neutral	None	None	None	None	N
Y/M	0.494	ambiguous	0.4608	ambiguous	-1.794	Destabilizing	0.974	D	0.654	neutral	None	None	None	None	N
Y/N	0.3345	likely_benign	0.2894	benign	-2.419	Highly Destabilizing	0.801	D	0.625	neutral	N	0.50316542	None	None	N
Y/P	0.9896	likely_pathogenic	0.9841	pathogenic	-2.576	Highly Destabilizing	0.974	D	0.673	neutral	None	None	None	None	N
Y/Q	0.5568	ambiguous	0.4594	ambiguous	-2.377	Highly Destabilizing	0.974	D	0.647	neutral	None	None	None	None	N
Y/R	0.4937	ambiguous	0.3688	ambiguous	-1.398	Destabilizing	0.949	D	0.661	neutral	None	None	None	None	N
Y/S	0.1752	likely_benign	0.1484	benign	-2.887	Highly Destabilizing	0.007	N	0.487	neutral	N	0.361039947	None	None	N
Y/T	0.3445	ambiguous	0.299	benign	-2.661	Highly Destabilizing	0.728	D	0.642	neutral	None	None	None	None	N
Y/V	0.349	ambiguous	0.3146	benign	-2.576	Highly Destabilizing	0.525	D	0.613	neutral	None	None	None	None	N
Y/W	0.4867	ambiguous	0.4108	ambiguous	-0.72	Destabilizing	0.998	D	0.654	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.