TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30602	92029;92030;92031	chr2:178550034;178550033;178550032	chr2:179414761;179414760;179414759
N2AB	28961	87106;87107;87108	chr2:178550034;178550033;178550032	chr2:179414761;179414760;179414759
N2A	28034	84325;84326;84327	chr2:178550034;178550033;178550032	chr2:179414761;179414760;179414759
N2B	21537	64834;64835;64836	chr2:178550034;178550033;178550032	chr2:179414761;179414760;179414759
Novex-1	21662	65209;65210;65211	chr2:178550034;178550033;178550032	chr2:179414761;179414760;179414759
Novex-2	21729	65410;65411;65412	chr2:178550034;178550033;178550032	chr2:179414761;179414760;179414759
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-149
• Domain position: 71
• Structural Position: 159
• Q(SASA): 0.5061
• Predicted PPI site: I

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/N	None	None	0.998	N	0.665	0.338	0.268660756437	gnomAD-4.0.0	1.59638E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87059E-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
K/A	0.2562	likely_benign	0.3119	benign	-0.17	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	I
K/C	0.4386	ambiguous	0.5046	ambiguous	-0.206	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
K/D	0.6214	likely_pathogenic	0.6947	pathogenic	0.075	Stabilizing	0.999	D	0.675	neutral	None	None	None	None	I
K/E	0.173	likely_benign	0.2086	benign	0.086	Stabilizing	0.994	D	0.584	neutral	N	0.467391912	None	None	I
K/F	0.6069	likely_pathogenic	0.6969	pathogenic	-0.398	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
K/G	0.3873	ambiguous	0.4709	ambiguous	-0.401	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
K/H	0.2186	likely_benign	0.2521	benign	-0.871	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
K/I	0.2369	likely_benign	0.2956	benign	0.367	Stabilizing	0.997	D	0.77	deleterious	N	0.475744824	None	None	I
K/L	0.2838	likely_benign	0.3594	ambiguous	0.367	Stabilizing	0.992	D	0.668	neutral	None	None	None	None	I
K/M	0.1953	likely_benign	0.2314	benign	0.425	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
K/N	0.4173	ambiguous	0.5097	ambiguous	0.218	Stabilizing	0.998	D	0.665	neutral	N	0.516975371	None	None	I
K/P	0.9636	likely_pathogenic	0.9737	pathogenic	0.217	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
K/Q	0.0973	likely_benign	0.1099	benign	-0.054	Destabilizing	0.999	D	0.694	prob.neutral	N	0.468240061	None	None	I
K/R	0.0666	likely_benign	0.0703	benign	-0.072	Destabilizing	0.994	D	0.577	neutral	N	0.45656163	None	None	I
K/S	0.3044	likely_benign	0.3725	ambiguous	-0.37	Destabilizing	0.983	D	0.584	neutral	None	None	None	None	I
K/T	0.1196	likely_benign	0.1443	benign	-0.199	Destabilizing	0.543	D	0.414	neutral	N	0.42739073	None	None	I
K/V	0.1895	likely_benign	0.2321	benign	0.217	Stabilizing	0.998	D	0.674	neutral	None	None	None	None	I
K/W	0.5955	likely_pathogenic	0.6737	pathogenic	-0.319	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
K/Y	0.5432	ambiguous	0.6158	pathogenic	0.047	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	I

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.