TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17449	52570;52571;52572	chr2:178608666;178608665;178608664	chr2:179473393;179473392;179473391
N2AB	15808	47647;47648;47649	chr2:178608666;178608665;178608664	chr2:179473393;179473392;179473391
N2A	14881	44866;44867;44868	chr2:178608666;178608665;178608664	chr2:179473393;179473392;179473391
N2B	8384	25375;25376;25377	chr2:178608666;178608665;178608664	chr2:179473393;179473392;179473391
Novex-1	8509	25750;25751;25752	chr2:178608666;178608665;178608664	chr2:179473393;179473392;179473391
Novex-2	8576	25951;25952;25953	chr2:178608666;178608665;178608664	chr2:179473393;179473392;179473391
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: Fn3-14
• Domain position: 81
• Structural Position: 112
• Q(SASA): 0.0941
• 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/K	rs1165942763	-0.72	0.958	D	0.687	0.407	0.246215685461	gnomAD-2.1.1	1.62E-05	None	None	None	None	N	None	0	1.16741E-04	None	0	0	None	0	None	0	0	0
N/K	rs1165942763	-0.72	0.958	D	0.687	0.407	0.246215685461	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	1.31199E-04	0	0	0	None	0	0	0	0	0
N/K	rs1165942763	-0.72	0.958	D	0.687	0.407	0.246215685461	gnomAD-4.0.0	7.70394E-06	None	None	None	None	N	None	0	1.0194E-04	None	0	0	None	0	0	0	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
N/A	0.9991	likely_pathogenic	0.9994	pathogenic	-1.31	Destabilizing	0.968	D	0.741	deleterious	None	None	None	None	N
N/C	0.9865	likely_pathogenic	0.9907	pathogenic	-0.944	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
N/D	0.9926	likely_pathogenic	0.995	pathogenic	-2.333	Highly Destabilizing	0.067	N	0.313	neutral	D	0.540136317	None	None	N
N/E	0.9992	likely_pathogenic	0.9994	pathogenic	-2.108	Highly Destabilizing	0.938	D	0.555	neutral	None	None	None	None	N
N/F	0.9998	likely_pathogenic	0.9999	pathogenic	-0.987	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
N/G	0.9958	likely_pathogenic	0.9969	pathogenic	-1.635	Destabilizing	0.968	D	0.522	neutral	None	None	None	None	N
N/H	0.994	likely_pathogenic	0.9955	pathogenic	-1.184	Destabilizing	0.998	D	0.705	prob.neutral	D	0.553267049	None	None	N
N/I	0.9981	likely_pathogenic	0.9987	pathogenic	-0.45	Destabilizing	0.994	D	0.767	deleterious	D	0.553520538	None	None	N
N/K	0.9992	likely_pathogenic	0.9994	pathogenic	-0.513	Destabilizing	0.958	D	0.687	prob.neutral	D	0.552253091	None	None	N
N/L	0.9955	likely_pathogenic	0.9969	pathogenic	-0.45	Destabilizing	0.995	D	0.778	deleterious	None	None	None	None	N
N/M	0.9967	likely_pathogenic	0.9976	pathogenic	-0.367	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
N/P	0.9996	likely_pathogenic	0.9997	pathogenic	-0.714	Destabilizing	0.995	D	0.769	deleterious	None	None	None	None	N
N/Q	0.9993	likely_pathogenic	0.9995	pathogenic	-1.167	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
N/R	0.9991	likely_pathogenic	0.9994	pathogenic	-0.611	Destabilizing	0.995	D	0.757	deleterious	None	None	None	None	N
N/S	0.9652	likely_pathogenic	0.9769	pathogenic	-1.426	Destabilizing	0.958	D	0.527	neutral	N	0.485303346	None	None	N
N/T	0.982	likely_pathogenic	0.9885	pathogenic	-1.051	Destabilizing	0.958	D	0.67	neutral	N	0.496428934	None	None	N
N/V	0.9977	likely_pathogenic	0.9984	pathogenic	-0.714	Destabilizing	0.995	D	0.776	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.01	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
N/Y	0.9972	likely_pathogenic	0.9978	pathogenic	-0.631	Destabilizing	0.998	D	0.749	deleterious	D	0.553267049	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.