TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5160	15703;15704;15705	chr2:178734346;178734345;178734344	chr2:179599073;179599072;179599071
N2AB	4843	14752;14753;14754	chr2:178734346;178734345;178734344	chr2:179599073;179599072;179599071
N2A	3916	11971;11972;11973	chr2:178734346;178734345;178734344	chr2:179599073;179599072;179599071
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-34
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1147
• 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
A/T	rs769431165	-1.501	1.0	D	0.661	0.446	0.510172456258	gnomAD-2.1.1	7.34E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.59E-05	0
A/T	rs769431165	-1.501	1.0	D	0.661	0.446	0.510172456258	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs769431165	-1.501	1.0	D	0.661	0.446	0.510172456258	gnomAD-4.0.0	6.25758E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.5422E-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
A/C	0.5567	ambiguous	0.66	pathogenic	-0.747	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
A/D	0.6084	likely_pathogenic	0.7219	pathogenic	-1.828	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
A/E	0.6282	likely_pathogenic	0.7387	pathogenic	-1.845	Destabilizing	1.0	D	0.833	deleterious	D	0.722409013	None	None	N
A/F	0.6807	likely_pathogenic	0.7781	pathogenic	-1.068	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/G	0.1244	likely_benign	0.1545	benign	-1.285	Destabilizing	1.0	D	0.551	neutral	D	0.531240631	None	None	N
A/H	0.813	likely_pathogenic	0.8834	pathogenic	-1.663	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
A/I	0.4955	ambiguous	0.6102	pathogenic	-0.415	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
A/K	0.8242	likely_pathogenic	0.892	pathogenic	-1.476	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
A/L	0.4426	ambiguous	0.5479	ambiguous	-0.415	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
A/M	0.4477	ambiguous	0.5679	pathogenic	-0.214	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/N	0.5401	ambiguous	0.6659	pathogenic	-1.132	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
A/P	0.9294	likely_pathogenic	0.9557	pathogenic	-0.576	Destabilizing	1.0	D	0.867	deleterious	D	0.613886777	None	None	N
A/Q	0.6871	likely_pathogenic	0.7845	pathogenic	-1.289	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
A/R	0.7867	likely_pathogenic	0.8465	pathogenic	-1.101	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/S	0.1114	likely_benign	0.1281	benign	-1.359	Destabilizing	1.0	D	0.574	neutral	D	0.526269853	None	None	N
A/T	0.1174	likely_benign	0.148	benign	-1.304	Destabilizing	1.0	D	0.661	neutral	D	0.630751937	None	None	N
A/V	0.2184	likely_benign	0.2763	benign	-0.576	Destabilizing	1.0	D	0.602	neutral	D	0.639811839	None	None	N
A/W	0.9392	likely_pathogenic	0.9683	pathogenic	-1.518	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
A/Y	0.7902	likely_pathogenic	0.8759	pathogenic	-1.129	Destabilizing	1.0	D	0.877	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.