TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8782	26569;26570;26571	chr2:178714430;178714429;178714428	chr2:179579157;179579156;179579155
N2AB	8465	25618;25619;25620	chr2:178714430;178714429;178714428	chr2:179579157;179579156;179579155
N2A	7538	22837;22838;22839	chr2:178714430;178714429;178714428	chr2:179579157;179579156;179579155
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-73
• Domain position: 47
• Structural Position: 115
• Q(SASA): 0.313
• 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
N/S	rs727504895	None	0.03	N	0.115	0.094	0.0846915920261	gnomAD-4.0.0	1.36848E-06	None	None	None	None	N	None	0	0	None	0	2.51915E-05	None	0	0	8.99501E-07	0	0
N/Y	rs1017848590	None	1.0	N	0.52	0.35	0.39724302092	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
N/Y	rs1017848590	None	1.0	N	0.52	0.35	0.39724302092	gnomAD-4.0.0	9.29567E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.1867E-05	0	1.60118E-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
N/A	0.2407	likely_benign	0.2497	benign	-0.883	Destabilizing	0.326	N	0.423	neutral	None	None	None	None	N
N/C	0.3865	ambiguous	0.413	ambiguous	0.097	Stabilizing	1.0	D	0.626	neutral	None	None	None	None	N
N/D	0.112	likely_benign	0.1145	benign	-0.136	Destabilizing	0.003	N	0.228	neutral	N	0.494918791	None	None	N
N/E	0.3729	ambiguous	0.3872	ambiguous	-0.11	Destabilizing	0.659	D	0.379	neutral	None	None	None	None	N
N/F	0.5371	ambiguous	0.5686	pathogenic	-0.985	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
N/G	0.253	likely_benign	0.2538	benign	-1.138	Destabilizing	0.837	D	0.402	neutral	None	None	None	None	N
N/H	0.1173	likely_benign	0.1194	benign	-1.039	Destabilizing	0.987	D	0.44	neutral	N	0.494553431	None	None	N
N/I	0.2673	likely_benign	0.3155	benign	-0.267	Destabilizing	0.997	D	0.578	neutral	N	0.456426129	None	None	N
N/K	0.2885	likely_benign	0.3263	benign	-0.055	Destabilizing	0.994	D	0.415	neutral	N	0.483141572	None	None	N
N/L	0.2722	likely_benign	0.2917	benign	-0.267	Destabilizing	0.995	D	0.554	neutral	None	None	None	None	N
N/M	0.3694	ambiguous	0.3992	ambiguous	0.32	Stabilizing	1.0	D	0.53	neutral	None	None	None	None	N
N/P	0.7293	likely_pathogenic	0.7299	pathogenic	-0.445	Destabilizing	0.955	D	0.509	neutral	None	None	None	None	N
N/Q	0.3378	likely_benign	0.3558	ambiguous	-0.675	Destabilizing	0.95	D	0.423	neutral	None	None	None	None	N
N/R	0.3161	likely_benign	0.339	benign	-0.006	Destabilizing	0.981	D	0.427	neutral	None	None	None	None	N
N/S	0.0864	likely_benign	0.0886	benign	-0.567	Destabilizing	0.03	N	0.115	neutral	N	0.491147767	None	None	N
N/T	0.1413	likely_benign	0.1388	benign	-0.361	Destabilizing	0.635	D	0.381	neutral	N	0.472617827	None	None	N
N/V	0.2847	likely_benign	0.3167	benign	-0.445	Destabilizing	0.945	D	0.579	neutral	None	None	None	None	N
N/W	0.7941	likely_pathogenic	0.8144	pathogenic	-0.761	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
N/Y	0.2031	likely_benign	0.2188	benign	-0.561	Destabilizing	1.0	D	0.52	neutral	N	0.465642841	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.