TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16506	49741;49742;49743	chr2:178613767;178613766;178613765	chr2:179478494;179478493;179478492
N2AB	14865	44818;44819;44820	chr2:178613767;178613766;178613765	chr2:179478494;179478493;179478492
N2A	13938	42037;42038;42039	chr2:178613767;178613766;178613765	chr2:179478494;179478493;179478492
N2B	7441	22546;22547;22548	chr2:178613767;178613766;178613765	chr2:179478494;179478493;179478492
Novex-1	7566	22921;22922;22923	chr2:178613767;178613766;178613765	chr2:179478494;179478493;179478492
Novex-2	7633	23122;23123;23124	chr2:178613767;178613766;178613765	chr2:179478494;179478493;179478492
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-7
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.7134
• 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/R	rs1206461113	0.197	0.001	N	0.223	0.064	0.1749357433	gnomAD-2.1.1	7.15E-06	None	None	None	None	I	None	4.14E-05	2.83E-05	None	0	0	None	0	None	0	0	0
K/R	rs1206461113	0.197	0.001	N	0.223	0.064	0.1749357433	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1206461113	0.197	0.001	N	0.223	0.064	0.1749357433	gnomAD-4.0.0	2.56686E-06	None	None	None	None	I	None	1.69451E-05	1.69589E-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	0.5463	ambiguous	0.4672	ambiguous	-0.016	Destabilizing	0.157	N	0.528	neutral	None	None	None	None	I
K/C	0.8909	likely_pathogenic	0.8046	pathogenic	-0.355	Destabilizing	0.909	D	0.6	neutral	None	None	None	None	I
K/D	0.7668	likely_pathogenic	0.7408	pathogenic	0.168	Stabilizing	0.567	D	0.513	neutral	None	None	None	None	I
K/E	0.3663	ambiguous	0.3631	ambiguous	0.189	Stabilizing	0.124	N	0.509	neutral	N	0.467264096	None	None	I
K/F	0.9231	likely_pathogenic	0.8775	pathogenic	-0.176	Destabilizing	0.726	D	0.577	neutral	None	None	None	None	I
K/G	0.6105	likely_pathogenic	0.5515	ambiguous	-0.221	Destabilizing	0.272	N	0.499	neutral	None	None	None	None	I
K/H	0.5432	ambiguous	0.4372	ambiguous	-0.382	Destabilizing	0.909	D	0.561	neutral	None	None	None	None	I
K/I	0.6661	likely_pathogenic	0.5794	pathogenic	0.445	Stabilizing	0.396	N	0.575	neutral	None	None	None	None	I
K/L	0.575	likely_pathogenic	0.5049	ambiguous	0.445	Stabilizing	0.157	N	0.51	neutral	None	None	None	None	I
K/M	0.4658	ambiguous	0.4002	ambiguous	0.104	Stabilizing	0.883	D	0.563	neutral	D	0.526351785	None	None	I
K/N	0.6263	likely_pathogenic	0.5868	pathogenic	0.099	Stabilizing	0.22	N	0.495	neutral	N	0.47946017	None	None	I
K/P	0.7343	likely_pathogenic	0.6405	pathogenic	0.32	Stabilizing	0.726	D	0.549	neutral	None	None	None	None	I
K/Q	0.2453	likely_benign	0.2064	benign	-0.023	Destabilizing	0.009	N	0.244	neutral	N	0.481576229	None	None	I
K/R	0.1014	likely_benign	0.0933	benign	-0.047	Destabilizing	0.001	N	0.223	neutral	N	0.470581092	None	None	I
K/S	0.6146	likely_pathogenic	0.5396	ambiguous	-0.403	Destabilizing	0.157	N	0.485	neutral	None	None	None	None	I
K/T	0.3064	likely_benign	0.2557	benign	-0.227	Destabilizing	0.001	N	0.273	neutral	N	0.467179762	None	None	I
K/V	0.6205	likely_pathogenic	0.5047	ambiguous	0.32	Stabilizing	0.396	N	0.491	neutral	None	None	None	None	I
K/W	0.9032	likely_pathogenic	0.8452	pathogenic	-0.199	Destabilizing	0.968	D	0.643	neutral	None	None	None	None	I
K/Y	0.8471	likely_pathogenic	0.7812	pathogenic	0.152	Stabilizing	0.726	D	0.584	neutral	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.