Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040128 | SCV000063819 | uncertain significance | not specified | 2012-07-24 | criteria provided, single submitter | clinical testing | The Pro9369Ala variant in TTN has not been reported in the literature nor previo usly identified by our laboratory. This variant has been identified in 1/8176 Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/), though this could represent a pre symptomatic individual. Computational analyses (biochemical amino acid propertie s, conservation, AlignGVGD, PolyPhen2, and SIFT) do not argue for or against an impact to the protein. Additional information is needed to fully assess the clin ical significance of the Pro9369Ala variant. |
Labcorp Genetics |
RCV000233950 | SCV000286572 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-12-27 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000725168 | SCV000334599 | uncertain significance | not provided | 2015-08-24 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000725168 | SCV000616056 | likely benign | not provided | 2018-10-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000725168 | SCV000730353 | likely benign | not provided | 2021-03-02 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 24503780) |
Ce |
RCV000725168 | SCV001152989 | likely benign | not provided | 2024-07-01 | criteria provided, single submitter | clinical testing | TTN: BP4 |
Illumina Laboratory Services, |
RCV001134533 | SCV001294280 | benign | Tibial muscular dystrophy | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Illumina Laboratory Services, |
RCV001134534 | SCV001294281 | uncertain significance | Early-onset myopathy with fatal cardiomyopathy | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001134535 | SCV001294282 | uncertain significance | Dilated cardiomyopathy 1G | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001135959 | SCV001295771 | benign | Myopathy, myofibrillar, 9, with early respiratory failure | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Illumina Laboratory Services, |
RCV001135960 | SCV001295772 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Baylor Genetics | RCV001135960 | SCV001525248 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2020-01-08 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040128 | SCV002599001 | likely benign | not specified | 2023-12-11 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.28105C>G (p.Pro9369Ala) results in a non-conservative amino acid change located in the I-band region of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00037 in 247188 control chromosomes, predominantly at a frequency of 0.00076 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. c.28105C>G has been reported in the literature in an individual affected with Dilated Cardiomyopathy and an individual reported with Sudden Unexplained Death (Pugh_2014, Campuzano_2015). These reports do not provide unequivocal conclusions about association of the variant with Dilated 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: 24503780, 26516846).Nine submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified as benign/likely benign (n=4) and VUS (n=5). Based on the evidence outlined above, the variant was classified as likely benign. |
Prevention |
RCV004528207 | SCV004103586 | uncertain significance | TTN-related disorder | 2023-03-13 | criteria provided, single submitter | clinical testing | The TTN c.28105C>G variant is predicted to result in the amino acid substitution p.Pro9369Ala. This variant has been reported in an individual with dilated cardiomyopathy and interpreted as uncertain significance (Table S3, referred to as g.179554549G>C/NM_133378.4:c.28105C>G, Pugh et al. 2014. PubMed ID: 24503780). This variant is reported in 0.077% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179554549-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |