Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040929 | SCV000064620 | uncertain significance | not specified | 2012-10-17 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Gln3191Glu vari ant in TTN has not been reported in the literature nor previously identified by our laboratory. It has been identified in 1/94 Han Chinese chromosomes from a b road population by the 1000 Genomes project (dbSNP rs33997263). Computational a nalyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Lys32641Gln variant may not impact the protein and se veral other species (including rat, birds, amphibians, and fish) carry a glutami c acid (Glu; this variant) despite high amino acid conservation nearby, suggesti ng that this variant may be tolerated, though this information is not predictive enough to rule out pathogenicity. This variant is more likely benign but at thi s time, additional information is needed to fully assess its clinical significan ce. |
Gene |
RCV000040929 | SCV000238063 | uncertain significance | not specified | 2014-07-08 | criteria provided, single submitter | clinical testing | Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in CARDIOMYOPATHY panel(s). |
Ambry Genetics | RCV000245580 | SCV000319090 | uncertain significance | Cardiovascular phenotype | 2013-09-20 | criteria provided, single submitter | clinical testing | The p.Q3191E variant (also known as c.9571C>G) is located in coding exon 40 of the TTN gene. This alteration results from a C to G substitution at nucleotide position 9571. The glutamine at codon 3191 is replaced by glutamic acid, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs33997263. Based on data from the 1000 Genomes Project, the G-allele has an overall frequency of approximately 0.05% (1/2184). The highest observed frequency was 0.52% (1/194) Han Chinese chromosomes studied. This amino acid position is poorly conserved on sequence alignment. This variant is predicted to be benign by PolyPhen in silico analyses. Since supporting evidence is limited at this time, the clinical significance of p.Q3191E remains unclear. |
Invitae | RCV000643340 | SCV000765027 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-11-12 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002496653 | SCV002784299 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 | 2021-08-25 | criteria provided, single submitter | clinical testing |