Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040762 | SCV007336393 | uncertain significance | not specified | 2025-10-21 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.82243G>A (p.Val27415Met) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 9.7e-05 in 248074 control chromosomes. This frequency is not significantly higher than estimated for disease-causing variants in TTN, allowing no conclusion about variant significance. c.82243G>A has been observed in individual(s) affected with Cardiomyopathy (Mazzarotto_2020, Mademont-Soler_2017, Pugh_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28771489, 31983221, 24503780). ClinVar contains an entry for this variant (Variation ID: 47493). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Baylor Genetics | RCV003147329 | SCV003835296 | uncertain significance | Early-onset myopathy with fatal cardiomyopathy | 2022-07-05 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000733290 | SCV003819205 | uncertain significance | not provided | 2019-03-27 | criteria provided, single submitter | clinical testing | |
| Athena Diagnostics | RCV000733290 | SCV002770564 | uncertain significance | not provided | 2021-07-16 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002362639 | SCV002660825 | likely benign | Cardiovascular phenotype | 2020-07-14 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Eurofins Ntd Llc |
RCV000733290 | SCV000861337 | uncertain significance | not provided | 2018-05-30 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000458878 | SCV000542543 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-11-21 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000040762 | SCV000064453 | uncertain significance | not specified | 2012-01-03 | criteria provided, single submitter | clinical testing | The Val27415Met variant (TTN) has not been previously reported nor previously id entified by our laboratory. Valine (Val) at position 27415 is highly conserved i n mammals and across evolutionarily distant species, increasing the likelihood t hat a change would not be tolerated. Computational predictions on the impact to the protein are mixed (AlignGVGD = benign, SIFT = pathogenic), though the accura cy of these tools is unknown. Additional information is needed to fully assess t he clinical significance of the Val27415Met variant. |
| Department of Clinical Pathology, |
RCV004558291 | SCV004218312 | likely benign | EBV-positive nodal T- and NK-cell lymphoma | no assertion criteria provided | research |