TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26944	81055;81056;81057	chr2:178565302;178565301;178565300	chr2:179430029;179430028;179430027
N2AB	25303	76132;76133;76134	chr2:178565302;178565301;178565300	chr2:179430029;179430028;179430027
N2A	24376	73351;73352;73353	chr2:178565302;178565301;178565300	chr2:179430029;179430028;179430027
N2B	17879	53860;53861;53862	chr2:178565302;178565301;178565300	chr2:179430029;179430028;179430027
Novex-1	18004	54235;54236;54237	chr2:178565302;178565301;178565300	chr2:179430029;179430028;179430027
Novex-2	18071	54436;54437;54438	chr2:178565302;178565301;178565300	chr2:179430029;179430028;179430027
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-139
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.5025
• 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/E	rs1199099522	0.414	0.892	N	0.428	0.252	0.301455362545	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/E	rs1199099522	0.414	0.892	N	0.428	0.252	0.301455362545	gnomAD-4.0.0	3.1831E-06	None	None	None	None	N	None	0	4.5731E-05	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
K/A	0.404	ambiguous	0.4158	ambiguous	0.071	Stabilizing	0.916	D	0.468	neutral	None	None	None	None	N
K/C	0.7554	likely_pathogenic	0.7423	pathogenic	-0.159	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
K/D	0.786	likely_pathogenic	0.7898	pathogenic	-0.047	Destabilizing	0.987	D	0.588	neutral	None	None	None	None	N
K/E	0.2789	likely_benign	0.3001	benign	-0.045	Destabilizing	0.892	D	0.428	neutral	N	0.485317873	None	None	N
K/F	0.8631	likely_pathogenic	0.8498	pathogenic	-0.175	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
K/G	0.545	ambiguous	0.5392	ambiguous	-0.11	Destabilizing	0.975	D	0.503	neutral	None	None	None	None	N
K/H	0.428	ambiguous	0.4194	ambiguous	-0.331	Destabilizing	0.997	D	0.589	neutral	None	None	None	None	N
K/I	0.4096	ambiguous	0.4147	ambiguous	0.467	Stabilizing	0.983	D	0.683	prob.neutral	N	0.506847938	None	None	N
K/L	0.4992	ambiguous	0.4977	ambiguous	0.467	Stabilizing	0.975	D	0.503	neutral	None	None	None	None	N
K/M	0.3367	likely_benign	0.3456	ambiguous	0.188	Stabilizing	0.999	D	0.584	neutral	None	None	None	None	N
K/N	0.6493	likely_pathogenic	0.6571	pathogenic	0.255	Stabilizing	0.967	D	0.515	neutral	N	0.473315843	None	None	N
K/P	0.7016	likely_pathogenic	0.6907	pathogenic	0.362	Stabilizing	0.996	D	0.577	neutral	None	None	None	None	N
K/Q	0.1856	likely_benign	0.1896	benign	0.1	Stabilizing	0.967	D	0.522	neutral	N	0.500191324	None	None	N
K/R	0.0727	likely_benign	0.0746	benign	0.008	Stabilizing	0.025	N	0.243	neutral	N	0.414148421	None	None	N
K/S	0.5579	ambiguous	0.5633	ambiguous	-0.17	Destabilizing	0.916	D	0.455	neutral	None	None	None	None	N
K/T	0.2682	likely_benign	0.2854	benign	-0.03	Destabilizing	0.967	D	0.52	neutral	N	0.455589982	None	None	N
K/V	0.4033	ambiguous	0.4051	ambiguous	0.362	Stabilizing	0.987	D	0.623	neutral	None	None	None	None	N
K/W	0.8177	likely_pathogenic	0.7977	pathogenic	-0.24	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
K/Y	0.7545	likely_pathogenic	0.7405	pathogenic	0.12	Stabilizing	0.996	D	0.632	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.