TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30182	90769;90770;90771	chr2:178552356;178552355;178552354	chr2:179417083;179417082;179417081
N2AB	28541	85846;85847;85848	chr2:178552356;178552355;178552354	chr2:179417083;179417082;179417081
N2A	27614	83065;83066;83067	chr2:178552356;178552355;178552354	chr2:179417083;179417082;179417081
N2B	21117	63574;63575;63576	chr2:178552356;178552355;178552354	chr2:179417083;179417082;179417081
Novex-1	21242	63949;63950;63951	chr2:178552356;178552355;178552354	chr2:179417083;179417082;179417081
Novex-2	21309	64150;64151;64152	chr2:178552356;178552355;178552354	chr2:179417083;179417082;179417081
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-148
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.4929
• 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
K/I	None	None	0.976	N	0.649	0.382	0.66885242914	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
K/A	0.3605	ambiguous	0.3554	ambiguous	-0.341	Destabilizing	0.863	D	0.496	neutral	None	None	None	None	N
K/C	0.6683	likely_pathogenic	0.684	pathogenic	-0.572	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
K/D	0.6768	likely_pathogenic	0.6555	pathogenic	0.359	Stabilizing	0.939	D	0.571	neutral	None	None	None	None	N
K/E	0.2143	likely_benign	0.1969	benign	0.425	Stabilizing	0.704	D	0.471	neutral	N	0.46587176	None	None	N
K/F	0.8207	likely_pathogenic	0.8245	pathogenic	-0.432	Destabilizing	0.997	D	0.651	neutral	None	None	None	None	N
K/G	0.5423	ambiguous	0.5388	ambiguous	-0.595	Destabilizing	0.969	D	0.587	neutral	None	None	None	None	N
K/H	0.3488	ambiguous	0.3423	ambiguous	-0.859	Destabilizing	0.991	D	0.583	neutral	None	None	None	None	N
K/I	0.3939	ambiguous	0.3896	ambiguous	0.268	Stabilizing	0.976	D	0.649	neutral	N	0.467085268	None	None	N
K/L	0.4234	ambiguous	0.4317	ambiguous	0.268	Stabilizing	0.939	D	0.596	neutral	None	None	None	None	N
K/M	0.2826	likely_benign	0.2894	benign	-0.006	Destabilizing	0.997	D	0.585	neutral	None	None	None	None	N
K/N	0.5011	ambiguous	0.4771	ambiguous	-0.108	Destabilizing	0.959	D	0.525	neutral	N	0.419176678	None	None	N
K/P	0.7976	likely_pathogenic	0.8079	pathogenic	0.093	Stabilizing	0.997	D	0.581	neutral	None	None	None	None	N
K/Q	0.134	likely_benign	0.1316	benign	-0.16	Destabilizing	0.31	N	0.292	neutral	N	0.463602246	None	None	N
K/R	0.0897	likely_benign	0.0899	benign	-0.183	Destabilizing	0.92	D	0.486	neutral	N	0.485593671	None	None	N
K/S	0.4271	ambiguous	0.4234	ambiguous	-0.728	Destabilizing	0.759	D	0.459	neutral	None	None	None	None	N
K/T	0.1644	likely_benign	0.1692	benign	-0.471	Destabilizing	0.061	N	0.351	neutral	N	0.420408829	None	None	N
K/V	0.3166	likely_benign	0.3253	benign	0.093	Stabilizing	0.939	D	0.587	neutral	None	None	None	None	N
K/W	0.8113	likely_pathogenic	0.8262	pathogenic	-0.385	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
K/Y	0.6801	likely_pathogenic	0.6822	pathogenic	-0.041	Destabilizing	0.997	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.